| 1. |
- Engel, Jörgen, 1942, et al.
(författare)
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Neonatal herpes simplex virus type 1 brain infection affects the development of sensorimotor gating in rats.
- 2000
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Ingår i: Brain research. - 0006-8993. ; 863:1-2, s. 233-40
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Tidskriftsartikel (refereegranskat)abstract
- The effect of neonatal brain infection of herpes simplex virus type 1 (HSV-1) on the development of sensorimotor function in the rat was investigated using an acoustic startle paradigm. Intracerebral inoculation of HSV-1 at day 2 after birth, but not at day 4, caused a significant delay in the development of prepulse inhibition of acoustic startle. A decrease in prepulse inhibition was shown at 37, 46 and 58 days of age in these rats compared to control rats. No evidence was obtained for other behavioural dysfunctions such as differences in sensorimotor reactivity, sensorimotor response habituation, spontaneous locomotor activity, rearing activity or stereotyped behaviour. Prepulse inhibition of acoustic startle is an accepted model of sensorimotor gating in the CNS, a function which has been shown diminished in schizophrenic persons. The present results suggest that early viral infections during a neurone-susceptible period may contribute to the development of this deficit.
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| 2. |
- Jerlhag, Elisabeth, 1978, et al.
(författare)
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Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens.
- 2008
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Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - : Elsevier BV. - 0924-977X. ; 18:7, s. 508-18
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we have reported that the orexigenic peptide ghrelin activates the cholinergic-dopaminergic reward link, involving nicotinic acetylcholine receptors (nAChR). The alpha(3)-alpha(7) and beta(2)-beta(4) subunits of the nAChR can be combined into pentameric nAChRs, with different functional roles. The present experiments show that the locomotor stimulatory effects of ghrelin, either into laterodorsal tegmental area (LDTg) or ventral tegmental area (VTA), are mediated via ventral tegmental nAChR, but neither the alpha(4)beta(2) (using dihydro-beta-erythroidine) nor the alpha(7) (using methyllycaconitine) subtypes appears to be involved. On the other hand, the alpha(3)beta(2), beta(3) and/or alpha(6) (using alpha-conotoxin MII) subtypes in the VTA mediate the stimulatory and DA-enhancing effects of ghrelin, a pattern that ghrelin shares with ethanol (n=5-8). Radioligand-binding experiments shown that ghrelin does not interfere directly with nAChRs (n=26). We therefore suggest that the alpha(3)beta(2), beta(3) and/or alpha(6) subtypes might be pharmacological targets for treatment of addictive behaviours including compulsive overeating and alcoholism.
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| 3. |
- Jerlhag, Elisabeth, 1978, et al.
(författare)
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Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward.
- 2006
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Ingår i: Addiction biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 11:1, s. 45-54
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Tidskriftsartikel (refereegranskat)abstract
- It is becoming increasingly apparent that there is a degree of neurochemical overlap between the reward systems and those regulating energy balance. We therefore investigated whether ghrelin, a stomach-derived and centrally derived orexigenic peptide, might act on the reward systems. Central ghrelin administration (1 microg/microL, to the third ventricle) induced an acute increase in locomotor activity as well as dopamine-overflow in the nucleus accumbens, suggesting that ghrelin can activate the mesoaccumbal dopamine system originating in the ventral tegmental area, a system associated with reward and motivated behaviour. The cholinergic afferents to the ventral tegmental area have been implicated in natural reward and in regulating mesoaccumbal dopamine neurons. The possibility that nicotinic receptors are involved in mediating the stimulatory and dopamine-enhancing effects of ghrelin is supported by the findings that peripheral injection of the unselective nicotinic antagonist mecamylamine (2.0 mg/kg) blocked these ghrelin-induced effects. Tentatively, ghrelin may, via activation of the acetylcholine-dopamine reward link, increase the incentive values of signals associated with motivated behaviours of importance for survival such as feeding behaviour. It will be important to discover whether this has therapeutic implications for compulsive addictive behaviours, such as eating behaviour disorders and drug dependence.
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| 4. |
- Narahashi, T, et al.
(författare)
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Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers.
- 2001
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Ingår i: Alcoholism, clinical and experimental research. - 0145-6008. ; 25:5 Suppl ISBRA, s. 152S-156S
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Forskningsöversikt (refereegranskat)abstract
- This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Bo Söderpalm. The presentations were (1) Nicotinic mechanisms and ethanol reinforcement: Behavioral and neurochemical studies, by Bo Söderpalm, M. Ericson, P. Olausson, and J. A. Engel; (2) Chronic nicotine and ethanol: Differential regulation in gene expression of nicotinic acetylcholine receptor subunits, by X. Zhang and A. Nordberg; (3) Nicotine-ethanol interactions at neuronal nicotinic acetylcholine receptors, by Toshio Narahashi, William Marszalec, and Gary L. Aistrup; (4) Relapse prevention in alcoholics by cigarette smoking? Treatment outcome in an observational study with acamprosate, by L.G. Schmidt, U. Kalouti, M. Smolka, and M. Soyka; and (5) Effect of nicotine on voluntary ethanol intake and development of alcohol dependence in male rats, by L. Hedlund and G. Wahlström.
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| 5. |
- Svensson, Anders I, 1969, et al.
(författare)
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Gonadectomy enhances shock-induced behavioral inhibition in adult male rats: implications for impulsive behavior.
- 2000
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Ingår i: Pharmacology, biochemistry, and behavior. - 0091-3057. ; 65:4, s. 731-6
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Tidskriftsartikel (refereegranskat)abstract
- The effects of gonadectomy on shock-induced behavioral inhibition in a modified Vogel's drinking conflict model and on diazepam-induced disinhibition and sedation were investigated in adult male rats. Gonadectomy enhanced shock-induced behavioral inhibition when determined 9, 21, 45, and 65 days, but not 3 days, after operation, without affecting shock sensitivity or drinking motivation. Testosterone-substitution for 21 days following gonadectomy prevented this enhanced inhibition without significantly affecting the behavior in sham-operated rats. Diazepam produced behavioral disinhibition both in sham-operated and gonadectomized rats. However, after the highest dose (16 mg/kg, IP) the disinhibited behavior decreased only in sham-operated animals, most likely due to sedation. Moreover, whereas there was no difference in basal rotarod-performance between controls and gonadectomized rats, the latter animals were less sensitive to diazepam-induced disruption of rotarod walking ability. Sham-operated or gonadectomized animals did not differ with respect to serum diazepam levels at the postinjection times used in the behavioral tests. Taken together, gonadectomized rats were less sensitive towards diazepam-induced sedation, possibly due to a subsensitivity at or beyond GABA(A)/benzodiazepine receptors. Furthermore, the finding that lack of testosterone enhanced shock-induced inhibition could be interpreted to reflect increased impulse control and may involve an altered activation of GABA(A)/benzodiazepine receptors.
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| 6. |
- Zhang, Jianhua, 1961, et al.
(författare)
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Involvement of the medial geniculate body in prepulse inhibition of acoustic startle.
- 1999
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Ingår i: Psychopharmacology. - 0033-3158. ; 141:2, s. 189-96
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Tidskriftsartikel (refereegranskat)abstract
- Prepulse inhibition of acoustic startle is the normal reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Previous studies have shown that several neuroanatomical structures and pathways in the brain are involved in the modulation of prepulse inhibition. In the present study, the functional importance of the medial geniculate body (MG) in the modulation of prepulse inhibition was investigated. To this end, in vivo brain microdialysis probes were used to infuse drugs locally into the MG of awake, freely moving rats simultaneously with startle response and prepulse inhibition measurements in the same animals. Intrageniculate infusion of the sodium channel blocker, tetrodotoxin, significantly reduced prepulse inhibition without affecting baseline startle amplitude. A similar effect was obtained after intrageniculate infusion of the GABA(B) receptor agonist, baclofen. In addition, intrageniculate infusion of muscimol, an agonist at the GABA(A) receptor complex, reduced prepulse inhibition, although this effect was obtained at a higher concentration of the drug compared to that of baclofen. These studies suggest that the MG is involved in the modulation of prepulse inhibition and that auditory signals relayed via the MG may be subjected to inhibitory control at this level, involving GABA neurotransmission.
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| 7. |
- Johnson, D H, et al.
(författare)
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Induction but not expression of behavioural sensitization to nicotine in the rat is dependent on glucocorticoids.
- 1995
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Ingår i: European journal of pharmacology. - 0014-2999. ; 276:1-2, s. 155-64
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Tidskriftsartikel (refereegranskat)abstract
- Behavioural sensitization has been implicated in the development of addictive behaviour, and several studies suggest that corticosteroids may be involved in this phenomenon. In the present study, the effects of adrenalectomy and steroid replacement treatments on the behavioural sensitization observed after daily injections of nicotine (0.4 mg/kg s.c.) were investigated in the rat. Adrenalectomy completely prevented sensitization to the locomotor stimulating effect of nicotine after repeated injections but did not influence the acute locomotor activating effect of the drug or an already established sensitization to nicotine. In adrenalectomized animals receiving replacement treatment with corticosterone or dexamethasone, but not aldosterone, repeated administration of nicotine produced behavioural sensitization. Repeated dexamethasone treatment per se failed, however, to sensitize rats to nicotine. Post mortem neurochemical studies showed that repeated administration of nicotine significantly increased homovanillic acid (HVA) levels, as well as the dihydroxyphenylacetic acid (DOPAC)/dopamine quotient, in the limbic forebrain. Adrenalectomy per se significantly increased HVA levels and tended to elevate the DOPAC/dopamine quotient. When repeatedly treated with nicotine, adrenalectomized rats displayed a higher DOPAC/dopamine quotient, but no significant difference in HVA levels, compared to nicotine-treated sham-operated controls. In the striatum and the cortex, no significant effects of nicotine treatment or adrenalectomy were observed on any of the neurochemical measures. The present results suggest that glucocorticoid (type II) receptor activation is required for induction of sensitization to the locomotor stimulatory effect of nicotine, whereas corticosteroids are not required for the expression of the behavioural sensitization once established. Provided that HVA levels and the DOPAC/dopamine quotient relatively well reflect the presynaptic dopamine activating effect of nicotine, it may be suggested that corticosteroid-related mechanisms associated with behavioural sensitization to nicotine are post- rather than presynaptically located in relation to mesolimbic dopamine neurons.
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| 8. |
- Lê, A D, et al.
(författare)
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Neurobiological processes in alcohol addiction.
- 2001
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Ingår i: Alcoholism, clinical and experimental research. - 0145-6008. ; 25:5 Suppl ISBRA, s. 144S-151S
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Forskningsöversikt (refereegranskat)abstract
- This article represents the proceedings of a symposium at the ISBRA Meeting in Yokohama, Japan. The chairs were A. D. Lê and K. Kiianmaa. The presentations were (1) Alcohol reward and aversion, by C. L. Cunningham; (2) The role of sensitization of neuronal mechanisms in ethanol self-administration, by J. A. Engel, M. Ericson, and B. Söderpalm; (3) Alcohol self-administration in dependent animals: Neurobiological mechanisms, by G. F. Koob, A. J. Roberts, and F. Weiss; (4) Stress and relapse to alcohol, by A. D. Lê; (5) Alcohol-preferring AA and alcohol-avoiding ANA rats differ in locomotor activation induced by repeated morphine injections, by P. Hyytiä, S. Janhunen, J. Mikkola, P. Bäckström, and K. Kiianmaa; and (6) Initial sensitivity and acute functional tolerance to the hypnotic effects of ethanol in mice genetically selected for mild and severe ethanol withdrawal convulsions, by I. Ponomarev and J. C. Crabbe.
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| 9. |
- Svensson, Anders I, 1969, et al.
(författare)
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Disinhibitory behavior and GABA(A) receptor function in serotonin-depleted adult male rats are reduced by gonadectomy.
- 2000
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Ingår i: Pharmacology, biochemistry, and behavior. - 0091-3057. ; 67:3, s. 613-20
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Tidskriftsartikel (refereegranskat)abstract
- Impulsive and aggressive behaviors in, e.g., personality or substance abuse disorders in man and corresponding behaviors in rats may involve serotonin (5-HT), gamma-amino-butyric acid(A)/benzodiazepine receptor complexes (GABA(A)/BDZ-RC) and steroid hormones, e.g., testosterone. Here, we studied the effect of gonadectomy on disinhibitory behavior in individually housed 5-HT-depleted rats and on GABA(A)/BDZ-RC function in vitro, in corticohippocampal synaptoneurosomes prepared from the brain of these animals. 5-HT depletion by intracerebroventricular 5,7-dihydroxytryptamine (5,7-DHT)-induced disinhibitory behavior in a shock-induced behavioral inhibition model (punished conflict model) 14 days after operation. Gonadectomy in connection with the 5-HT depletion reduced the disinhibitory behavior and testosterone substitution prevented this effect. Shock threshold and drinking motivation were not affected by gonadectomy and/or 5-HT depletion. The relative epididymides weight was increased in 5-HT-depleted as compared to sham-operated rats. However, the serum concentrations of testosterone and the relative testes weights were not different in 5-HT-depleted rats as compared to controls. GABA-induced (30, 100, 300 microM) 36Cl(-)-uptake into synaptoneurosomes was lower in 5,7-DHT+gonadectomized rats compared to the control group. This effect was reversed by substitution with testosterone. These results demonstrate that gonadectomy reduces disinhibitory behavior in 5-HT-depleted rats and that GABA(A)/BDZ-RC may be involved in this effect.
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| 10. |
- Svensson, Anders I, 1969, et al.
(författare)
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Testosterone treatment induces behavioral disinhibition in adult male rats.
- 2003
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Ingår i: Pharmacology, biochemistry, and behavior. - 0091-3057. ; 75:2, s. 481-90
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Tidskriftsartikel (refereegranskat)abstract
- The importance of testosterone for impulsive-like behavior is unclear. Here we studied the effect of testosterone administration during 6 and 14 days (separate experiments) with one, three and five testosterone-filled silastic capsules implanted subcutaneously on shock-induced behavioral inhibition and on flunitrazepam-induced disinhibition in a modified Vogel's drinking conflict model in rats. Alleviation of shock-induced behavioral inhibition has been suggested to reflect impulsive-like behavior and/or anxiolysis. Treatment with the highest testosterone dose used for 6 (Experiment 1) and 14 (Experiment 3) days increased the number of shocks accepted. Testosterone treatment affected serum levels of testosterone and accessory sex organ weights. Flunitrazepam induced behavioral disinhibition in both testosterone-treated (for 14 days) and sham-treated rats. Moreover, testosterone treatment for 14 days resulted in enhanced GABA-induced 36Cl- uptake into synaptoneurosomes as compared to controls. In conclusion, testosterone produces behavioral disinhibition and may enhance brain GABAA receptor function.
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