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Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Pharmacology)
2000 (English)In: Alcohol, ISSN 0741-8329, E-ISSN 1873-6823, Vol. 22, no 3, 165-171 p.Article in journal (Refereed) Published
Abstract [en]

Recently, we have shown that rats repeatedly treated with ethanol and/or cocaine have decreased kappa-opioid receptor mRNA levels in the mesolimbic system. The aim of the present study was to investigate the short- and long-term effects of repeated ethanol administration on opioid peptide concentrations in brain tissue of male Sprague-Dawley rats. Dynorphin B (1-13) (Dyn B) and Met-enkephalinArg(6)Phe(7) (MEAP), endogenous ligands to kappa- and delta-opioid receptors, respectively, were measured using radioimmunoassays. The rats were given either ethanol [intraperitoneal (ip), twice daily, 2 g/kg bw/dose] or saline for 13 consecutive days. Thirty minutes after the last ethanol dose on Day 13, the Dyn B tissue concentration was significantly decreased in the cingulate cortex. The MEAP tissue concentration was decreased in the hippocampus 5 days after the last ethanol injection as compared to saline-treated controls. Furthermore, the Dyn B and the MEAP concentrations were increased in the periaqueductal grey area (PAG) at this time point. Of particular interest were the significant increases in Dyn B tissue concentrations found in the nucleus accumbens (NAcc) at 30 min and at 21 days after the last ethanol dose. The results suggest that repeated ethanol administration induces both short- and long-term changes in the tissue concentrations of opioids in certain brain regions associated with motivation and reward.

Place, publisher, year, edition, pages
2000. Vol. 22, no 3, 165-171 p.
Keyword [en]
opioids, nucleus accumbens, dynorphin B, ethanol, Met-enkephalinArg(6)Phe(7)
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-51076DOI: 10.1016/S0741-8329(00)00118-XISI: 000166492200007PubMedID: 11163124OAI: oai:DiVA.org:uu-51076DiVA: diva2:78985
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Involvement of the Opioid System in High Alcohol Consumption: Environmental and Genetic Influences
Open this publication in new window or tab >>Involvement of the Opioid System in High Alcohol Consumption: Environmental and Genetic Influences
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It is well accepted that both inherent and environmental factors influence the pathogenesis of alcohol dependence. This thesis investigates the role of the opioid system in the initiation and maintenance of high ethanol intake. Ethanol-preferring C57BL/6J mice differ from ethanol-avoiding DBA/2J mice in that they exhibit lower basal levels of the opioid peptides dynorphin B and Met-enkephalin-Arg6Phe7 (MEAP) in the nucleus accumbens, which may contribute to their divergent drug-taking behaviour. Chronic ethanol intake in C57BL/6J mice and repeated ethanol administration in Sprague-Dawley rats induce time-specific changes in dynorphin B and MEAP levels in regions, such as the nucleus accumbens and the ventral tegmental area, associated with reinforcing effects of drugs of abuse.

Daily neonatal handling for 15 min (H15) and maternal separation for 360 min (MS360) during postnatal day 1-21 were used as models for environmental manipulation early in life. H15 in male rats results in decreased anxiety-like behaviour, whereas MS360 increases anxiety-like behaviour. Both H15 and MS360 induce changes in dynorphin B and MEAP levels especially in regions related to the hypothalamic-pituitary-adrenal (HPA) axis. In female rats, regions related to the HPA axis are unaffected by H15. This suggests a gender-specific involvement of opioids in the HPA axis response to stress. More rats in the MS360 group initiate ethanol consumption and have a higher ethanol intake later in life than the H15 group. The H15 group has particularly low ethanol intake and also differs with regard to neurochemistry compared to both MS360 and control groups, suggesting that H15 can induce long-term changes, protective against high ethanol intake. Specific changes in opioid receptor density are observed after chronic ethanol consumption, such as an increased κ-receptor density in several brain areas, as well as changes in δ-receptor density in the frontal cortex and the nucleus accumbens. Altogether, these results suggest that the opioid system plays an important role in the mechanisms underlying the initiation and maintenance of high ethanol intake.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 72 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 264
Keyword
Pharmaceutical biosciences, Opioids, ethanol, stress, maternal separation, neonatal handling, Farmaceutisk biovetenskap
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Pharmacology
Identifiers
urn:nbn:se:uu:diva-1653 (URN)91-554-5217-5 (ISBN)
Public defence
2002-03-01, B41, Uppsala, 09:15 (English)
Opponent
Available from: 2002-02-06 Created: 2002-02-06 Last updated: 2009-06-02Bibliographically approved

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