| 1. |
- Haage, David, et al.
(författare)
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Allopregnanolone modulates spontaneous GABA release via presynaptic Cl- permeability in rat preoptic nerve terminals
- 2002
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 958:2, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- The endogenous neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) affects presynaptic nerve terminals and thereby increases the frequency of spontaneous GABA release. The present study aimed at clarifying the mechanisms underlying this presynaptic neurosteroid action, by recording the frequency of spontaneous GABA-mediated inhibitory postsynaptic currents (sIPSCs) in neurons from the medial preoptic nucleus (MPN) of rat. Acutely dissociated neurons with functional adhering nerve terminals were studied by perforated-patch recording under voltage-clamp conditions. It was shown that the sIPSC frequency increased with the external K(+) concentration ([K(+)](o)). Further, the effect of allopregnanolone on the sIPSC frequency was strongly dependent on [K(+)](o). In a [K(+)](o) of 5 mM, 2.0 microM allopregnanolone caused a clear increase in sIPSC frequency. However, the effect declined rapidly with increased [K(+)](o) and at high [K(+)](o) allopregnanolone reduced the sIPSC frequency. The effect of allopregnanolone was also strongly dependent on the external Cl(-) concentration ([Cl(-)](o)). In a reduced [Cl(-)](o) (40 mM, but with a standard [K(+)](o) of 5 mM), the effect on sIPSC frequency was larger than that in the standard [Cl(-)](o) of 146 mM. The dependence of the effect of allopregnanolone on [K(+)](o) and on estimated presynaptic membrane potential was also altered by the reduction in [Cl(-)](o). As in standard [Cl(-)](o), the effect in low [Cl(-)](o) declined when [K(+)](o) was raised, but reversed at a higher [K(+)](o). The GABA(A) receptor agonist muscimol also potentiated the sIPSC frequency. Altogether, the results suggest that allopregnanolone exerts its presynaptic effect by increasing the presynaptic Cl(-) permeability, most likely via GABA(A) receptors.
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| 2. |
- Anderson, Kevin J., et al.
(författare)
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Ischemia-induced upregulation of excitatory amino acid transport sites
- 1993
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Ingår i: Brain Research. - 0006-8993. ; 622:1-2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- The response of excitatory amino acid transporter binding sites in the rat brain to 10 min of cerebral ischemia induced by bilateral common carotid occlusion combined with hypotension was examined. We observed a transient increase in the density of transporter binding sites that was first noticeable at 5 min post-recovery and persisted for 48 h. The increase in binding sites was found throughout the brain, but was most prevalent in hippocampus and other cortical regions. We conclude that delayed neuronal death following transient cerebral ischemia may not be due to a decrease in the number of excitatory amino acid transport sites.
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| 3. |
- Bassant, M H, et al.
(författare)
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Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants in the rat brain
- 1988
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 460:1, s. 8-16
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Tidskriftsartikel (refereegranskat)abstract
- Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants were studied in adult rats anesthetized with urethane. No specific topography of the neurons recorded was observed within the graft. The mean spontaneous activity of the grafted neurons (GNs) was relatively low (4.9 impulses/s) but not unlike that of other central neurons in situ. A large proportion of GNs fired with regular discharges, but other modes of discharge were also observed. A few rhythmically bursting GNs were recorded having a discharge pattern very much like that of the rhythmically bursting medial septal neurons. The responses of GNs to glutamate, gamma-aminobutyric acid, acetylcholine, serotonin and norepinephrine was fairly similar to those described in other central structures.
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| 4. |
- Bengzon, Johan, et al.
(författare)
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Regulation of norepinephrine transporter and tyrosine hydroxylase mRNAs after kainic acid-induced seizures
- 1999
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Ingår i: Brain Research. - 0006-8993. ; 842:1, s. 239-242
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Tidskriftsartikel (refereegranskat)abstract
- Noradrenergic locus coeruleus (LC) efferents to the forebrain suppress seizures in several models of epilepsy. Using in situ hybridization, we demonstrate that tyrosine hydroxylase (TH) and norepinephrine transporter (NET) but not vesicular monoamine transporter 2 (VMAT2) mRNA levels are transiently elevated in LC neurons following kainic acid-induced status epilepticus. These increases of TH and NET mRNAs and presumably of the proteins themselves might enhance synthesis and reuptake of NE postictally.
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| 5. |
- Blay, Pilar, et al.
(författare)
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An in vivo study of the effect of 5-HT and sympathetic nerves on transferrin and transthyretin mRNA expression in rat choroid plexus and meninges
- 1994
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 662:1-2, s. 148-154
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Tidskriftsartikel (refereegranskat)abstract
- Brain expression of transferrin (Tf) and transthyretin (TTR) mRNA has been demonstrated in different species, TTR being found only in the choroid plexus. We report here that both these mRNAs are also expressed in the meninges. In vitro studies have shown that Tf secretion by the rat choroid plexus is stimulated by 5-hydroxytryptamine (5-HT) while sympathetic nerves regulate different transport functions in the same tissue. We have used various in vivo models to study the neuroendocrine regulation of Tf and TTR mRNA expression in the choroid plexus and meninges. Destruction of the serotonergic nerves in the brain by either raphe nuclei lesion or intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), which both decreased brain 5-HT levels significantly, did not affect Tf or TTR mRNA levels in choroid plexus and meninges, but increased TTR mRNA in liver. Intraventricular injection of 10 or 100 pmol 5-HT did not change the expression of these proteins in any of the tissues studied. Removal of the sympathetic innervation to the choroid plexus by cervical sympathectomy did not affect Tf or TTR mRNA levels in choroid plexus and liver, nor the incorporation of radioactive leucine into protein in various parts of the brain. In conclusion, our results do not support a regulatory role in vivo for neuronally derived 5-HT or sympathetic nerve activity on Tf and TTR mRNA expression in rat choroid plexus and meninges.
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| 6. |
- Cervero, F., et al.
(författare)
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Cutaneous inputs to dorsal horn neurones in adult rats treated at birth with capsaicin
- 1984
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 301:1, s. 47-57
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Tidskriftsartikel (refereegranskat)abstract
- Single unit electrical activity has been recorded from dorsal horn neurons in the lumbar spinal cord of adult rats which had been treated at birth with either capsaicin (50 mg kg-1) or with the solvent-vehicle only. The responses of these neurones to electrical stimulation of A- and C-fibres in the sural nerve and to natural stimulation of their cutaneous receptive fields have been studied. In vehicle-injected rats, 54% of the units driven by electrical stimulation of the A-fibres in the sural nerve could also be driven by stimulation of the C-fibers in this nerve. In capsaicin-treated animals, only 30% of such units had a C-fibre input from the sural nerve. In vehicle-injected rats, 51.5% of the neurones with a C-fibre input showed a 'wind-up' effect on repetitive C-fibre stimulation of the sural nerve at 1 Hz. A similar proportion of neurones (55%) displayed this effect in capsaicin-treated rats. There were fewer neurones with very intense 'wind-up' in capsaicin-treated compared to vehicle-treated rats. In capsaicin-treated animals, greater proportions of neurones with 'wind-up' were superficially located in the dorsal horn, had small receptive fields and were driven only by cutaneous nociceptors. The proportions of neurones driven by innocuous mechanical stimulation of the skin, by noxious mechanical stimulation or by both forms of stimulation were similar in vehicle-injected and capsaicin-treated animals. In capsaicin-treated rats, more neurones had 'medium-sized' receptive fields than in vehicle-injected rats. In capsaicin-treated rats, more neurones had receptive fields in the foot and ankle than in vehicle-injected animals, where receptive fields in the toes were predominant. Some neurones showed expanded receptive fields after repetitive electrical stimulation of C-fibres at 1 Hz. This expansion occurred more often in neurones recorded from capsaicin-treated animals than in those of vehicle-injected rats. These results are discussed in relation to the role of afferent C-fibres in sensory mechanisms.
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| 7. |
- Chang, Jing-Yu, et al.
(författare)
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Serotonin uptake into cerebrovascular nerve fibers of rat, visualization by immunohistochemistry, disappearance following sympathectomy, and release during electrical stimulation
- 1989
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 492:1-2, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemistry as well as in vitro uptake and release of [3H]5-HT were performed on pial arteries of rat to investigate the nature of 5-HT containing nerve fibers. Immunoreactive fibers were constantly found only in the basilar, vertebral and superior cerebellar arteries, while in the other parts of the circle of Willis, 5-HT immunofluorescent fibers were absent. After systemic treatment with tryptophan following inhibition of monoamine oxidase with nialamide the immunofluorescence intensity was markedly enhanced. The 5-HT immunoreactive fibers disappeared after superior cervical ganglionectomy or intraventricular administration of 6-hydroxydopamine, but persisted after administration of 5,6-dihydroxytryptamine. When isolated vessels were incubated in low concentration of 5-HT (1 nM) together with nialamide, a very dense plexus of 5-HT immunoreactive fibers appeared in all branches of the circle of Willis. Uptake and release experiments were carried out by incubation of arterial preparations with 3 nM [3H]5-HT (together with nialamide), followed by electrical field stimulation, or by exposure to tyramine or 124 mM potassium, all of which induced a 100%-350% increase in the tritium release over prestimulation values. Preincubation with cocaine and bilateral superior cervical ganglionectomy abolished or markedly attenuated the release upon all modes of stimulation. The results suggested that the 5-HT observed by immunohistochemistry in pial arteries is located in sympathetic nerve terminals where it may serve as a neuromodulator that is released during nerve activation.
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| 8. |
- Duan, W M, et al.
(författare)
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Methylprednisolone prevents rejection of intrastriatal grafts of xenogeneic embryonic neural tissue in adult rats
- 1996
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 712:2, s. 199-212
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Tidskriftsartikel (refereegranskat)abstract
- We studied the effects of high-dose methylprednisolone on the survival of intrastriatal neural xenografts and the host responses against them. Dissociated mesencephalic tissue from inbred mouse (CBA-strain) embryos was transplanted to the intact striatum of adult Sprague-Dawley rats. The rats received either daily injections of methylprednisolone (30 mg/kg), or cyclosporin A (10 mg/kg), or no immunosuppressive treatment. Two or six weeks after transplantation, there was good survival of xenografts in both the methylprednisolone- and cyclosporin A-treated rats. In contrast, the xenografts in untreated control rats were all rejected by six weeks. There was no marked difference in the degree of expression of MHC class I and II antigens and the accumulation of activated astrocytes and microglial cells/macrophages between the three groups. However, both methylprednisolone and cyclosporin A reduced infiltration of T lymphocytes to the transplantation sites. The expression of pro-inflammatory cytokines (interferon-gamma, tumour necrosis factor-alpha, interleukin-6) in and around the grafts was lower in the methylprednisolone- and cyclosporin A-treated groups than in untreated control rats. Although high-dose methylprednisolone caused significant body weight loss, we conclude that this treatment can prevent rejection of intrastriatal grafts of xenogeneic embryonic neural tissue in the adult.
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| 9. |
- Edbladh, M., et al.
(författare)
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Insulin and IGF-II, but not IGF-I, stimulate the in vitro regeneration of adult frog sciatic sensory axons
- 1994
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 641:1, s. 76-82
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Tidskriftsartikel (refereegranskat)abstract
- We used the in vitro regenerating frog sciatic nerve to look for effects of insulin and insulin-like growth factors I and II (IGF-I, IGF-II) on regeneration of sensory axons and on injury induced support cell proliferation in the outgrowth region. In nerves cultured for 11 days, a physiological dose (10 ng/ml, ≈ nM) of insulin or IGF-II increased ganglionic protein synthesis (by 20% and 50%, respectively) as well as the level of newly formed, radiolabelled axonal material distal to a crush injury (both by 80%), compared to untreated, paired controls. In addition, insulin increased the outgrowth distance of the furthest regenerating sensory axons by 10%. The preparation was particularly sensitive to insulin during the first 5 days of culturing. Furthermore, both insulin and IGF-II were found to inhibit proliferation of support cells in the outgrowth region in a manner suggesting effects via their individual receptors. The inhibition, about 30%, was observable after 4 but not 11 days in culture. It is not clear if this reflects a stimulated differentiation of some cells. By contrast, IGF-I lacked effects on both regeneration and proliferation. In conclusion, the results suggest that insulin and IGF-II are involved in the regulation of peripheral nerve regeneration.
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| 10. |
- Edström, Anders, et al.
(författare)
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Adenosine inhibition of the regeneration in vitro of adult frog sciatic sensory axons
- 1992
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Ingår i: Brain Research. - 0006-8993. ; 570:1-2, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- The sensory axons of the adult frog sciatic nerve have earlier been shown to regenerate in vitro. If a local test crush is made at the initiation of culturing, regeneration starts after 3.4 days and proceeds at a rate of about 0.8-0.9 mm/day for several days. In the present experiments regeneration was inhibited by adenosine in a reversible and dose-dependent fashion. Similarly, both an adenosine analogue, 2-chloroadenosine (2-CA), and a non-hydrolyzable ATP analogue, AMP-PNP, reduced the outgrowth of sensory axons. The effect of adenosine was partially antagonized by theophylline at a critical concentration. Using a compartmental system, it could clearly be shown that adenosine exerted its effects at the outgrowth region. Adenosine, 2-CA, and AMP-PNP were also found to inhibit the proliferation of Schwann cells in the regenerating nerve. Various experiments showed that the latter can not explain the outgrowth inhibitory effects, which could be mediated by adenosine receptors associated with the elongating axons.
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| 11. |
- Edström, Anders, et al.
(författare)
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Moderate elevation of extracellular potassium transiently inhibits regeneration of sensory axons in cultured adult sciatic nerves
- 1995
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Ingår i: Brain Research. - 0006-8993. ; 693:1-2, s. 148-154
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Tidskriftsartikel (refereegranskat)abstract
- The adult frog dorsal root ganglia (DRG) together with the sciatic nerve (ScN) has previously been shown to survive in organ culture for several days. If a local test crush is made at the beginning of culturing, there is an initial delay of about 3 days before the sensory axons start to grow into the distal nerve stump at a rate of about 0.6-0.9 mm/day. The present results showed that axonal growth was unaffected in preparations maintained for 8 days in medium containing 10 mM K+ (5 mM is the physiological level). In contrast, the outgrowth was markedly reduced by 15 mM K+ and still more by 20 and 25 mM K+. The growth inhibition was partially counteracted by nifedipine, a Ca2+-channel antagonist. Other experiments clearly showed that high K+ exerted its effects during the early phase of the regeneration and lacked effects at later stages. The possibility that Ca2+-binding proteins, e.g., calbindin, which showed immunohistochemical reactivity in different structures, contribute to the growth adaptation to high K+ will be considered. The generality of the findings was supported by inhibition of axonal outgrowth of adult mouse sciatic sensory axons by high K+.
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| 12. |
- Edström, Anders, et al.
(författare)
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The use of the regenerating frog sciatic nerve for pharmacological studies of orthograde and retrograde axonal transport
- 1987
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 401:1, s. 34-42
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Tidskriftsartikel (refereegranskat)abstract
- The outgrowth region of the regenerating frog sciatic nerve shows an increased permeability for various drugs, which has been utilized for pharmacological studies of axonal transport. Six days after a bilateral crush lesion, the nerves, including the spinal ganglia, were incubated in a compartmented chamber. Orthograde transport was assessed from the proximodistal distribution and the accumulation of labelled proteins in the nerve growth region. Retrograde transport was examined by allowing orthogradely transported materials to reverse at the regenerating region and then to accumulate at a ligature during a second incubation period. The distribution of radioactivity along the nerve was assayed by fluorography of whole-mount nerve preparations or by scintillation counting. Fluorography made it possible to increase the spatial resolution and to demonstrate effects in the elongating part of the regenerating nerve. Colchicine at low concentrations (10-100 μM) only inhibited axonal transport in the outgrowth region (6 mm long at 6 days after crush) and along some mm of the nerve proximal to the crush. Compound 48/80 (50 μg/ml), the most specific calmodulin inhibitor so far described, inhibited the transport along the same part of the nerve. Cytochalasin B (10 μg/ml) inhibited transport by effects limited to the outgrowth region. Both orthograde and retrograde transport showed sensitivity to these and some other drugs. The regenerating frog sciatic nerve seems to have significant advantages for pharmacological studies of axonal transport.
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| 13. |
- Ekström, Per A R, et al.
(författare)
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Nerve regeneration and serum levels of insulin-like growth factor-I in rats with streptozotocin-induced insulin deficiency
- 1989
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 496:1-2, s. 141-147
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral nerve regeneration was studied in female Sprague-Dawley rats with streptozotocin-induced insulin deficiency. Nerve regeneration was provoked by a crush lesion on the sciatic nerve 21 days after the streptozotocin injection. The regeneration was assessed by a pinch test at different time-points after injury. The rate ofregeneration in insulin-deficient animals, 2.5 mm/day, was significantly lower than in control animals, 2.9 mm/day(P < 0.05). There was no difference in the initial delay, i.e. the period before regeneration attains a constant velocity. One group of insulin-deficient rats was treated with insulin during the regeneration period by means of implanted osmotic mini-pumps. This treatment prevented the decrease in regenerationsw. After 6 days the sciatic nerves of insulin-deficient rats had regenerated 12.3 ±0.3 mm (mean ±S.E.M.), while the corresponding value for insulin-treated rats was 15.7 ±0.6 mm (P > 0.01). The streptozotocin-treated rats were found to have a 39% reduction in the serum level of insulin-like 1 growth factor-I (IGF-I)_compared to control rats (0.33 ± 0.22 μg/ml and 0.54 ± ml respectively, (P < 0.001). Insulin treatment 1830 1732 during the regeneration period completely restored the IGF-I level back to normal.
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| 14. |
- Ekström, Peter, et al.
(författare)
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GABA and GABA-transporter (GAT-1) immunoreactivities in the retina of the salmon (Salmo salar L.)
- 1998
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Ingår i: Brain Research. - 0006-8993. ; 812:1-2, s. 179-185
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Tidskriftsartikel (refereegranskat)abstract
- Putative GABAergic elements in the retina of the Atlantic salmon have been identified by immunohistochemistry, utilising polyclonal antisera against γ-aminobutyric acid (GABA) and the GABA transporter GAT-1. Cell types immunoreactive (ir) for GABA comprise horizontal cells, amacrine cells, displaced amacrine cells in the ganglion cell layer, displaced amacrine cells in the inner plexiform layer (interstitial cells), and Muller cells. In addition, a GABA-immunonegative type of interstitial cell was also identified. In the inner plexiform layer, GABAir fibres were organised in sublayers that were strikingly similar to the sublayering of GAT-1ir fibres. GAT-lir cell bodies comprise amacrine cells and displaced amacrine cells that may represent a subpopulation of the GABAir ones. In view of the very similar sublayering of GABAir and GAT-ir fibres in the IPL we suggest that a similar type of GABA transporter, that can be recognised with antibodies against rat GAT-1, is present at least in the dendrites of all GABAir amacrine cells but is not expressed in the cell bodies of all GABAir cells.
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| 15. |
- Elmer, Eskil, et al.
(författare)
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Delayed kindling development after rapidly recurring seizures: relation to mossy fiber sprouting and neurotrophin, GAP-43 and dynorphin gene expression
- 1996
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 712:1, s. 19-34
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Tidskriftsartikel (refereegranskat)abstract
- Development of kindling and mossy fiber sprouting, and changes of gene expression were studied after 40 seizures produced during about 3 h by electrical stimulation every 5 min in the ventral hippocampus. As assessed by 5 test stimulations, enhanced responsiveness was present already after 6-24 h but from 1 week post-seizure increased gradually up to 4 weeks without additional stimuli. Sprouting of mossy fibers in the dentate gyrus was demonstrated only at 4 weeks with Timm's staining. In situ hybridization showed a transient increase (maximum at 2 h) of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), TrkB and TrkC mRNA levels and reduction (maximum at 12-24 h) of neurotrophin-3 (NT-3) mRNA expression in dentate granule cells after the seizures. In addition, BDNF mRNA levels were elevated in CA1 and CA3 regions, amygdala and piriform cortex. Marked increases of mRNA for growth-associated protein (GAP-43), with maximum expression at 12-24 h, were observed in dentate granule cells and in amygdala-piriform cortex. Dynorphin mRNA levels showed biphasic changes in dentate granule cells with an increase at 2 h followed by a decrease at 24 h. No long-term alterations of gene expression were observed. These findings indicate that increased responsiveness develops rapidly after recurring seizures but that the kindled state is reached gradually in about 4 weeks. Mossy fiber sprouting occurs in parallel to epileptogenesis and may play a causative role. Short-term changes of neurotrophin and Trk, GAP-43 and dynorphin mRNA levels and the assumed alterations of the corresponding proteins could trigger structural rearrangements underlying kindling but might also contribute to the initial increase of seizure susceptibility.
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| 16. |
- Fischer, W, et al.
(författare)
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In vivo acetylcholine release as measured by microdialysis is unaltered in the hippocampus of cognitively impaired aged rats with degenerative changes in the basal forebrain
- 1991
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 556:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- Acetylcholine (ACh) release was studied in awake, freely moving animals using in vivo microdialysis in the hippocampus of young (3-month-old) and aged (24-month-old) female Sprague-Dawley rats. Two groups of aged rats were selected on basis of their spatial learning performance in the Morris water maze: non-impaired aged rats which performed as well as the young control animals, and impaired aged rats which learnt the task very poorly. Baseline ACh overflow (in the presence of 5 microM neostigmine) was 1.9 +/- 0.3 +/- pmol/15 min in the young animals and 1.6 +/- 0.4 pmol/15 min in both the impaired and the non-impaired aged rats; these levels did not differ from each other. Depolarization by KCl (100 mM) or muscarinic receptor blockade by atropine (3 microM) added to the perfusion fluid produced dramatic, 4-6-fold, increases in ACh overflow that was similar in magnitude in both the young and the aged impaired and non-impaired rats. Behavioral activation by either handling or electrical stimulation of the lateral habenula produced 2-3-fold increases in extracellular ACh-levels in the hippocampus similarly in all three groups. The results indicate that hippocampal ACh release is maintained in aged rats that exhibit severe spatial learning and memory impairments and that the septo-hippocampal cholinergic system retains its capacity to increase its ACh release in response to both K(+)-induced depolarization and behavioral activation in the aged rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 17. |
- Grabowski, Martin, et al.
(författare)
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Sensorimotor performance and rotation correlate to lesion size in right but not left hemisphere brain infarcts in the spontaneously hypertensive rat
- 1991
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 547:2, s. 249-257
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Tidskriftsartikel (refereegranskat)abstract
- In order to correlate behavioural deficits to lesion size and to reveal possible functional asymmetries in the rat brain, locomotor activity, rotation and sensorimotor integration to touch were studied in spontaneously hypertensive rats (SHR) subjected to right or left middle cerebral artery occlusion. Control and infarcted rats showed no difference in locomotor activity. Infarcted rats tended to rotate towards the side of the lesion. A large sensorimotor deficit was found contralateral to the infarcted hemisphere. The absolute values of the side-biases for the rotation and sensorimotor tests were of the same degree irrespective of lesion side. Whereas the left hemisphere lesion size did not correlate to the behavioural outcome, the size of the right hemisphere lesion was highly correlated to the total sensorimotor deficit. Furthermore, the sensorimotor deficit of specific body parts was found to correlate to the damage of certain brain regions in a rostrocaudal fashion, reminiscent of a somatotopical organization. The extent of ipsilateral rotation correlated to brain tissue loss at the level of the posterior caudate-putamen. The present results indicate an asymmetrical organization for brain functions involved in the performance of the rotation and sensorimotor tests.
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| 18. |
- Holmqvist, Bo, et al.
(författare)
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Subcellular localization of neuronal nitric oxide synthase in the brain of a teleost; an immunoelectron and confocal microscopical study
- 1997
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Ingår i: Brain Research. - 0006-8993. ; 745:1-2, s. 67-82
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Tidskriftsartikel (refereegranskat)abstract
- The subcellular localization of neuronal nitric oxide (NO) synthase (NOS)-immunoreactive (NOSir) elements in the brain of the Atlantic salmon was investigated by means of electron microscopy and confocal laser scanning microscopy. NOSir structures are present only in neuronal elements. In neuronal processes, strong NOS immunoreactivity was mainly localized within synaptic vesicles or seen as a dense accumulation associated with the plasma membrane of dendrites and at terminal formations. NOSir precipitate was also associated with microtubuli and mitochondrial outer membranes. The highest accumulation of NOS immunoreactivity was found in dendrites located in close apposition to immunonegative myelinated or unmyelinated neural processes. Several NOSir and unmyelinated immunonegative profiles formed synaptic specializations. Immunonegative neurons in contact with NOSir processes always contained round clear synaptic vesicles. In neuronal somata, strong NOS immunoreactivity was localized in the cristae of some large mitochondria, whereas vacuoles and the endoplasmic reticulum showed a relatively weak staining. Confocal microscopic analysis of NOS immunofluorescence showed a corresponding subcellular localization of NOS in different brain regions, but also indicated the presence of NOS axosomatic terminals. Our data show that specific neurons contain a neuronal NOS-like molecule which to a high degree is stored in vesicles and is accumulated at various sites along the neuronal processes or at specific synaptic terminal formations. Thus, NO may be formed and exert its actions at various sites along the processes of NOS-synthesizing neurons. The present study provides evidence at the ultrastructural level that NO may play a messenger role in neural circuits involved in visual and hypophysiotrophic brain functions.
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| 19. |
- Jongsma, Helen, et al.
(författare)
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Alteration of PACAP distribution and PACAP receptor binding in the rat sensory nervous system following sciatic nerve transection
- 2000
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Ingår i: Brain Research. - 0006-8993. ; 853, s. 96-186
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely expressed neuropeptide that has been involved in nerve regeneration, neurone survival and nociception. In this study, the distribution of PACAP and PACAP-receptors were investigated in rat dorsal root ganglia (DRG), spinal cord and medulla oblongata at 3, 7 or 14 days following unilateral sciatic nerve transection using immunohistochemistry, 125I-PACAP-binding and in situ hybridisation. In control (contralateral side) DRG, about 30% of the nerve cell bodies (92% being small) were PACAP-immunoreactive (PACAP-IR). In the spinal cord, PACAP-IR fibres were seen in laminae I-II but not in the gracile nuclei. Following sciatic nerve transection, PACAP-IR fibres appeared in the gracile nuclei and occasionally in the deeper laminae of the dorsal horn consistent with the relative increase in larger PACAP-IR DRG neurones. However, the relative number of small PACAR-IR neurones was significantly lower on the transected side as compared to the control side suggesting a dual reaction for PACAP in the DRG following nerve injury. 125I-PACAP-binding was found in laminae I-II, around the central canal and in the gracile nuclei but not in the DRG. At 14 days after transection, 125I-PACAP-binding density was significantly reduced in the ipsilateral dorsal horn. PACAP-receptor (PAC(1)) mRNA was detected in neurones of the dorsal and ventral horn and in the gracile nuclei with no overt changes observed after transection. Very few DRG nerve cell bodies contained PAC(1) mRNA. The findings are consistent with a role for PACAP both in nociception and regeneration.
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| 20. |
- Kanje, Martin, et al.
(författare)
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Ca2+-activated protease activity in frog sciatic nerve : Characterization and effect on rapidly transported axonal proteins
- 1985
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 327:1-2, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Protease activity was studied in the frog sciatic nerve. The activity was measured as the release of TCA-soluble radioactivity from either 3H-labelled proteins transported by rapid axonal transport (AXT) or 3H-labelled ganglionic proteins. In nerve homogenates containing transported substrates, protease activity exhibited two peaks, one around pH 5 and one around pH 8. Ca2+ at 100 μM or higher concentrations only stimulated the latter, which was inhibited by 1 mM parachloromercuric benzoate, a sulphydryl reagent, but unaffected by ATP (1 mM). The proteolytic activity was recovered in the 105 g supernatant of the homogenate. In desheathed nerves containing 3H-labelled transported proteins, the protease activity could be activated by exposing the nerve to a Ca2+-ionophore, X-537 A, or to an elevated Ca2+-concentration (50 mM). These conditions were also shown to increase the influx and efflux of 45Ca2+ in the nerves. The results indicate the presence within axons of a Ca2+-activated soluble protease, which degrades rapidly transported proteins. The finding that the protease degraded ganglionic soluble proteins to about the same extent suggests a broad substrate specificity. The present system should be useful for further characterization of protease activity during various physiological conditions.
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| 21. |
- Kanje, Martin, et al.
(författare)
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Divalent cations and fast axonal transport in chemically desheathed (triton X-treated) frog sciatic nerve
- 1982
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Ingår i: Brain Research. - 0006-8993. ; 241:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the ability of divalent cations to restore to normal axonal transport (AXT) which was inhibited by deprivation of Ca2+ and/or Mg2+ ions. The epi- and perineurium of the frog sciatic nerve were damaged by a 30-s wash in Triton X-100 containing frog Ringer's. This treatment did not affect either AXT or nerve levels of Ca2+ and Mg2+, but made the ions more easily extractable with a Ca2+- and Mg2+-free Ringer's solution (CMFR). Inhibition of AXT was achieved by incubating Triton X-100-treated nerves in CMFR + EGTA for 5 h, followed by an additional incubation for 12 h in CMFR or Ringer's devoid of only Ca2+ (CFR). These treatments reduced Ca2+ and Mg2+ contents by 77% and 38% respectively. Addition of Ca2+ (1.1 mM) during the 12-h period stimulated AXT, measured as accumulation of 3H-labelled components in front of a ligature, several fold. Mg2+ could not substitute for Ca2+ but potentiated the stimulating effect of Ca2+. Addition of other divalent cations did not affect AXT (Sr2+ and Ba2+) or potentiated the inhibition caused by Ca2+-deprived medium (Mn2+ and Co2+). ATP and creatine phosphate contents were similar in nerves incubated in Ca2+-deprived medium and in Ca2+-containing Ringer's. Thus, inhibition of AXT in the former situation was not due to a decreased availability of high energy phosphates. Two calcium antagonists, D-600 and nifedipin, which are potent smooth muscle relaxants, effectively blocked AXT. The present ressults suggest that Ca2+ is specifically required to maintain AXT and that an anlogy exists between Ca2+ regulation during smooth muscle contraction and AXT.
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| 22. |
- Katsura, Ken Ichiro, et al.
(författare)
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Acidosis enhances translocation of protein kinase C but not Ca2+/calmodulin-dependent protein kinase II to cell membranes during complete cerebral ischemia
- 1999
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Ingår i: Brain Research. - 0006-8993. ; 849:1-2, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- Systemic hyperglycemia and hypercapnia severely aggravate ischemic brain damage when instituted prior to cerebral ischemia. An aberrant cell signaling following ischemia has been proposed to be involved in ischemic cell death, affecting protein kinase C (PKC) and the calcium calmodulin kinase II (CaMKII). Using a cardiac arrest model of global brain ischemia of 10 min duration, we investigated the effect of hyperglycemia (20 mM) and hypercapnia (pCO2 300 mmHg) on the subcellular redistribution of PKC (α, β, γ) and CaMKII to synaptic membranes and to the microsomes, as well as the effect on PKC activity. We confirmed the marked translocation of PKC and CaMKII to cell membranes induced by ischemia, concomitantly with a decrease in the PKC activity in both the membrane fraction and cytosol. Hyperglycemia and hypercapnia markedly enhanced the translocation of PKC-γ to cell membranes while other PKC isoforms were less affected. There was no effect of acidosis on PKC activity, or on translocation of CaMKII to cell membranes. Our data strongly suggest that the enhanced translocation of PKC to cell membranes induced by hyperglycemia and hypercapnia may contribute to the detrimental effect of tissue acidosis on the outcome following ischemia. Copyright (C) 1999 Elsevier Science B.V.
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| 23. |
- Leanza, G, et al.
(författare)
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Compensatory changes of in vivo acetylcholine and noradrenaline release in the hippocampus after partial deafferentation, as monitored by microdialysis
- 1993
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 615:1, s. 147-159
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Tidskriftsartikel (refereegranskat)abstract
- Lesions of the fimbria-fornix pathways are known to induce a partial cholinergic and noradrenergic denervation of the hippocampal formation, which is followed by a slow and protracted collateral sprouting by the spared afferents. Using the intracerebral microdialysis technique, compensatory changes in extracellular levels of acetylcholine (ACh) and noradrenaline (NA) have been monitored over time in the partially denervated hippocampus of awake unrestrained rats subjected to an unilateral fimbria-fornix (FF) transection. One week after the lesion, baseline ACh output was reduced by 90% and 80% in the dorsal and ventral hippocampus, respectively, and it remained depressed still by 6 months after lesion. KCl-evoked and atropine-stimulated ACh efflux were equally reduced by 1 week after lesion, remained depressed at 3 months, but showed a significant recovery by 6 months post-lesion. Tissue choline acetyltransferase (ChAT) activity levels, initially reduced by 92% and 86%, in the dorsal and ventral hippocampus, respectively, recovered significantly by 3 months and remained unchanged at 6 months. Baseline NA output was significantly reduced (-80%) in the dorsal hippocampus by 1 week after the lesion and showed a partial recovery over time (to 50% of normal), whereas the ventral part was not significantly affected by the FF lesion. The significant FF lesion-induced reduction in KCl- or desipramine (DMI)-stimulated NA release observed in the dorsal hippocampus at 1 week after the lesion remained unchanged during the subsequent months. By contrast, in the ventral hippocampus, the initial 65-70% reduction in KCl- and DMI-stimulated NA release significantly recovered to normal levels within 3 months post-lesion. The NA tissue levels were significantly reduced by 4 weeks after lesion, in the dorsal hippocampus and did not show any significant recovery over time. In the ventral hippocampus, these levels were significantly reduced only at 4 weeks. Transmitter turnover, expressed as the ratio between dialysate levels and tissue ChAT or NA content, showed a 3-fold increase in the dorsal hippocampus at 4 weeks after lesion, but not at later time points. This indicates that the spared noradrenergic and cholinergic afferents respond to the partial denervation by a transient increase in transmitter turnover, evident as early as 4 weeks post-lesion in the region of maximal denervation. This was followed by a long-term increase in evoked transmitter release which may result from a slowly progressing compensatory sprouting of the spared afferents.
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| 24. |
- Leanza, G, et al.
(författare)
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Functional activity of intrahippocampal septal grafts is regulated by catecholaminergic host afferents as studied by microdialysis of acetylcholine
- 1993
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 618:1, s. 47-56
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Tidskriftsartikel (refereegranskat)abstract
- Previous microdialysis experiments have shown that acetylcholine (ACh) release from septal grafts in the hippocampus of awake rats is influenced by the behaviour of the animals, which strongly suggests that the host brain can exert a regulatory control over the activity of the grafted neurons. Since the activity of the normal septo-hippocampal cholinergic system is likely to be regulated, in part, by brainstem catecholaminergic afferents, we wished to study the effect of catecholaminergic drugs on ACh release in the hippocampus reinnervated by septal grafts. Rats were subjected to a unilateral aspirative fimbria-fornix (FF) transection and grafted with tissue from the fetal septal-diagonal band area, either as a cell suspension injection into the depth of the hippocampus or as a solid implant in the FF lesion cavity. Microdialysis of ACh release was carried out 17-20 months after transplantation in awake, freely-moving animals. The reduction in steady-state ACh overflow induced by the FF lesion (-81%) was restored to normal or above normal levels in rats with either solid or suspension grafts. In normal rats, systemic administration of apomorphine (2.0 mg/kg, s.c.) or amphetamine (2.5 mg/kg, i.p.) caused a 3.7 (+189%) or 7.8 (+301%) pmol/15 min increase in ACh overflow compared to the previous baseline level, respectively. The drug-induced increases in ACh levels in the FF-lesioned controls was substantially lower than normal (86-89% reduction). Both apomorphine and amphetamine resulted in an approximately two-fold increase in hippocampal ACh release in rats with suspension grafts. These responses were significantly increased over those seen in rats with FF lesions only, but they tended to be lower and more variable than normal. Rats with solid septal grafts responded significantly stronger than FF lesion controls to amphetamine with two-fold increased ACh overflow, whereas the response to apomorphine was less clear-cut. Pretreatment with the catecholamine synthesis blocker alpha-methyl-p-tyrosine (AMPT; 200 mg/kg x 3) did not affect steady-state or apomorphine-stimulated release of ACh in any of the groups, whereas the effect of amphetamine was abolished in both normal and grafted rats. The results suggest that ACh release derived from septal grafts in the hippocampus, similar to the normal septo-hippocampal system, can be affected by manipulations of the host catecholaminergic systems. This mechanism may, at least in part, underlie the ability of the host brain to influence and control the activity of grafted cholinergic neurons.
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| 25. |
- Mandel, R J, et al.
(författare)
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Amphetamine induces excess release of striatal acetylcholine in vivo that is independent of nigrostriatal dopamine
- 1994
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 653:1-2, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- The effect of amphetamine on striatal acetylcholine (ACh) release was studied by an in vivo intrastriatal microdialysis technique. Although we expected systemic amphetamine to inhibit baseline striatal ACh release, the opposite was found. In addition, we found that the amphetamine-induced striatal ACh release did not depend on nigrostriatal DA since 6-hydroxydopamine (6-OHDA) lesions had no effect on amphetamine-induced ACh release. Local intrastriatal injection of amphetamine via the microdialysis probe had no effect on striatal ACh release even when the probe was located more laterally in striatum to take advantage of the medial to lateral gradient of striatal ACh and D2 receptors. The hypothesis that amphetamine increased extracellular striatal ACh by increasing the release of biogenic amines besides dopamine was tested by pharmacological manipulations designed to specifically increase local striatal norepinephrine or serotonin levels. The serotonergic and noradrenergic manipulations had no effect on striatal ACh levels. These results indicate that amphetamine-induced release of ACh in striatum is mediated via distal brain regions that are functionally connected with the striatum.
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