| 1. |
- Cappendijk, Susanne L T, et al.
(författare)
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A heroin-, but not a cocaine expecting, self-administration state preferentially alters brain endogenous peptides
- 1999
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Ingår i: European Journal of Pharmacology. - 0014-2999 .- 1879-0712. ; 365:2-3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the current study was to assess neuropeptidergic alterations during a phase of the drug addiction cycle associated with drug craving as compared to a time period when the drug had been recently self-administered. Male Wistar rats were allowed to self-administer cocaine, heroin or saline for 6 h for 5 consecutive days. Immediately following the last self-administration session ('acute drug on board' state), and just before the next scheduled session ('drug expecting' state), the animals were decapitated and the levels of dynorphin A and B, [Met5]- and [Leu5]-enkephalin and substance P were measured in different brain areas. During the 'acute drug on board' state, peptide levels in animals that self-administered heroin or cocaine were not significantly changed. In contrast, during the 'drug expecting' state, heroin-treated animals had increased levels of dynorphin A, dynorphin B and [Met5]-enkephalin in the caudal striatum as compared to the cocaine- and saline-treated animals, and the level of [Leu5]-enkephalin was increased as compared to the cocaine-treated group. In the septum, an increase of [Met5]-enkephalin and substance P was observed in the animals expecting heroin as compared to the saline- and/or cocaine-treated animals. In the caudal striatum, substance P levels were elevated in the heroin- and cocaine-expecting animals. In conclusion, heroin, as compared to cocaine, appears to have a more pronounced effect on dynorphin, enkephalin and substance P levels in the caudal striatum and septum, especially during periods when self-administration of the drug is expected.
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| 2. |
- Franck, Johan, et al.
(författare)
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Met-enkephalin inhibits 5-hydroxytryptamine release from the rat ventral spinal cord via delta opioid receptors
- 1996
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908 .- 1873-7064. ; 35:6, s. 743-749
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Tidskriftsartikel (refereegranskat)abstract
- The effect of opioid receptor agonists and antagonists on the electrically evoked release of endogenous serotonin (5-hydroxytryptamine, 5-HT) was studied in superfused slices of the rat ventral lumbar spinal cord. Met-ENK (1 x 10(-8)M-1 x 10(-6)M) and DPDPE (1 x 10(-8)M-1 x 10(-6)M) reduced the evoked 5-Ht release in a concentration dependent fashion. DAMGO (1 x 10(-8)-1 x 10(-6)) and (-)-trans-(1S,2S)-U-50488 (1 x 10(-6)M) had no effect on the 5-HT release. The inhibitory effect of met-ENK was completely abolished by ICI-174,864, but neither by naloxonazine nor nor-binaltorphimine. Following i.c.v. treatment with 5,7-dihydroxytryptamine (5,7-DHT), the tissue concentration of 5-HT was reduced by 97%, whereas the concentration of noradrenaline was reduced by only 5%. The tissue concentration of met-ENK, as measured by radioimmunoassay, was not significantly altered. The results suggest that met-ENK is present in the rat ventral spinal cord mainly in non-serotonergic nerve terminals and exerts an inhibitory action on 5-HT release via delta opioid receptors.
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| 3. |
- Herrera-Marschitz, M, et al.
(författare)
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On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis
- 1996
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 66:4, s. 1726-1735
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Tidskriftsartikel (refereegranskat)abstract
- Several putative neurotransmitters and metabolites were monitored simultaneously in the extracellular space of neostriatum, substantia nigra, and cortex and in subcutaneous tissue of the rat by in vivo microdialysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and gamma-aminobutyric acid (GABA) was at nanomolar concentrations in all brain regions. The highest concentration of dopamine (DA) was in the neostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutaneous tissue, Glu and Asp levels were 5 and approximately 5 and approximately 0.4 microM, respectively. Lactate and pyruvate concentrations were approximately 200 and approximately 10 microM in all regions. The following criteria were applied to ascertain the neuronal origin of substances quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) depletion of presynaptic vesicles by local administration of alpha-latrotoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In contrast, Glu and Asp levels were not greatly affected by K+ depolarization and were increased by perfusing with tetrodotoxin or with Ca2+-free medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-depolarizing conditions by alpha-latrotoxin. Because the effect of K+ depolarization on Glu and Asp could be masked by reuptake into nerve terminals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in the microdialysis perfusion medium. The effect of K+ depolarization on Glu and Asp levels was increased by DHKA, but GABA levels were also affected. In contrast, PDC increased only Glu levels. It is concluded that there is pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysis reflect the balance between neuronal release and reuptake into surrounding nerve terminals and glial elements.
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| 4. |
- Nylander, Ingrid, et al.
(författare)
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A comparison of microwave irradiation and decapitation. Basal levels of dynorphin and enkephalin peptides and the effect of morphine treatment on dynorphin peptides
- 1997
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Ingår i: Neuropeptides. - 0143-4179 .- 1532-2785. ; 31:4, s. 357-365
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Tidskriftsartikel (refereegranskat)abstract
- Opioid peptides were analysed in tissue extracts of various brain structures and the pituitary gland from rats sacrificed by microwave irradiation, and compared with peptide levels in tissue extracts from decapitated rats. Dynorphin A, dynorphin B and Leu-enkephalinArg6, derived from prodynorphin, and Met-enkephalinArg6Phe7 from proenkephalin, were measured. Basal immunoreactive levels of dynorphin A and B were consistently higher in extracts from microwave-irradiated rats, whereas in these extracts immunoreactive levels of Leu-enkephalinArg6, an endogenous metabolite of dynorphin peptides, were either lower than, the same as or higher than in decapitated rats. Immunoreactive levels of Met-enkephalinArg6Phe7 were higher in microwave-irradiated rats. Effects of morphine treatment on prodynorphin peptide levels were evaluated and compared with previous findings in decapitated rats. Dynorphin immunoreactive levels were higher in the nucleus accumbens and striatum of morphine-tolerant rats than in corresponding areas in saline-treated rats. These results indicate tissue-specific metabolism of prodynorphin peptides and show that metabolism of opioid peptides occurs during the dissection procedure after decapitation of the rat even though precautions are taken to minimize degradation.
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| 5. |
- Nylander, Ingrid, et al.
(författare)
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Opioid peptides in drug dependence and neurological diseases
- 1998
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Ingår i: Neurochemical markers of degenerative nervous diseases and drug addiction. - : VSP, Utrecht, The Netherlands. - 9067642770 - 978 90 67 64277 4 ; , s. 171-192
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Ploj, Karolina, et al.
(författare)
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Neonatal handling in rats induces long-term effects on dynorphin peptides
- 1999
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Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 33:6, s. 468-474
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Tidskriftsartikel (refereegranskat)abstract
- The effects of neonatal handling on the opioid dynorphin peptides in the brain and pituitary gland of Sprague-Dawley rats were investigated. Ten weeks after the neonatal handling, handled rats had higher tissue levels of dynorphin A and B in the hypothalamus, pituitary gland and striatum and slightly higher dynorphin B levels in the hippocampus, medulla oblongata and midbrain as compared with non-handled controls. The results indicate a persistent upregulation of the dynorphin system in certain brain areas after neonatal handling, which could contribute to the behavioural changes in these rats observed later in life. Observation in the open field and the elevated plus-maze tests confirmed behavioural effects of neonatal handling, i.e. showing that handled rats exhibit attenuated fearfulness in novel environments as compared with non-handled rats.
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| 7. |
- Sandin, Johan, et al.
(författare)
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Differential metabolism of dynorphins in substantia nigra, striatum and hippocampus
- 1997
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Ingår i: Peptides. - 0196-9781 .- 1873-5169. ; 18:7, s. 949-956
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Tidskriftsartikel (refereegranskat)abstract
- To map the proteolytic enzymes metabolizing dynorphins in brain structures, size-exclusion chromatography linked to electrospray ionization mass spectrometry was used. Enzymes extracted from rat hippocampus, striatum, and substantia nigra were tested for their capability of converting dynorphin-related peptides. Dynorphin A was the most resistant to proteolytic conversion, whereas Big dynorphin and dynorphin B-29 were slowly converted to dynorphin A and dynorphins A and B, respectively. Dynorphin B and alpha-neoendorphin were the least resistant. Dynorphin B was rapidly converted to Leu-enkephalin in the striatum and hippocampus but to Leu-enkephalin-Arg6 in the substantia nigra. alpha-Neoendorphin was converted to Leu-enkephalin in all tissues investigated.
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| 8. |
- Sandin, J, et al.
(författare)
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Hippocampal dynorphin B injections impair spatial learning in rats : a kappa-opioid receptor-mediated effect
- 1998
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Ingår i: Neuroscience. - 0306-4522 .- 1873-7544. ; 85:2, s. 375-382
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampus plays a central role in the acquisition and storage of information. Long-term potentiation in the mossy fibre pathway to the CA3 region in the hippocampus, an animal model of memory acquisition, is modulated by dynorphin peptides. This study investigated the possible role of hippocampal dynorphin in spatial learning. Male rats were trained in the Morris Water Task after microinjection with different doses of dynorphin B (1, 3.3 or 10 nmol/rat) or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Dynorphin B was found to impair spatial learning at all tested doses. The synthetic kappa1-selective opiate receptor antagonist nor-binaltorphimine (2 nmol) also given into the hippocampus fully blocked the acquisition impairment caused by dynorphin B (10 nmol), while nor-binaltorphimine alone did not affect learning performance. These findings suggest that dynorphin peptides could play a modulatory role in hippocampal plasticity by acting on hippocampal kappa-receptors and thereby impair spatial learning.
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| 9. |
- Sandin, Johan, et al.
(författare)
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Metabolism of beta-endorphin in plasma studied by liquid chromatography-electrospray ionization mass spectrometry
- 1998
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 73:1, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Degradation of synthetic human beta-endorphin by a human plasma proteinase was studied with high-performance liquid chromatography in combination with mass spectrometry. The peptide was metabolized at a rate of 25 pmol/min to the major fragments beta-endorphin (1-19) and (20-31), the latter reported as a potent inhibitor of morphine- and beta-endorphin-induced analgesia in mice. The proteinase responsible for this process was classified as a metal-dependent serine proteinase and was effectively inactivated by phenylmethylsulfonyl fluoride and ethylenediaminetetraacetic acid. Identification of the products formed during the enzymatic reaction was performed by liquid chromatography on-line with electrospray mass spectrometry, using a reversed-phase or a novel size-exclusion column capable of separating molecules between 0.1-7 kilodaltons. Peptide sequences were verified by tandem mass spectrometry experiments. The conversion of beta-endorphin may have physiological implications in the mechanism of pain. The obtained data suggest that several precautions should be considered during recovery and measurement of beta-endorphin in plasma by immunological techniques. The applied strategy may also be useful for studying metabolism of various peptidergic compounds with potential pharmacological significance.
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| 10. |
- Silberring, Jerzy, et al.
(författare)
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Characterization of immunoreactive dynorphin B and beta-endorphin in human plasma
- 1998
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Ingår i: Peptides. - 0196-9781 .- 1873-5169. ; 19:8, s. 1329-1337
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Tidskriftsartikel (refereegranskat)abstract
- Dynorphins and beta-endorphin in human plasma were characterized and studied quantitatively using radioimmunoassay, high-performance liquid chromatography (HPLC), and mass spectrometry. Most immunoreactive (ir) dynorphin B and beta-endorphin in human plasma coeluted with authentic peptides in analysis. Dynorphin A was not detected. Added to human plasma it was rapidly converted into Leu-enkephalin-Arg6 followed by elimination of the C-terminal arginine after prolonged incubation. The rate of dynorphin A conversion was estimated at 40 pmol/min/microl plasma. This process was inhibited by the thiol protease inhibitor, PHMB and by EDTA. Dynorphin B, alpha-neoendorphin and big dynorphin were virtually not metabolized by plasma proteases under the same conditions. beta-endorphin was processed into beta-endorphin(1-19) and the corresponding C-terminal counterpart beta-endorphin(20-31) at a rate of about 25 pmol/min/microl of plasma. Based on the above data, a reliable strategy was established to measure dynorphin B- and beta-endorphin-ir in human plasma samples. The basal levels in a male control group were 0.99 +/- 0.11 (n = 11) and 16.3 +/- 1.5 (n = 11) fmol/ml plasma, respectively.
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