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Effects of maternal separation on voluntary ethanol intake and brain peptide systems in female Wistar rats.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2005 (English)In: Pharmacol Biochem Behav, ISSN 0091-3057, Vol. 81, no 3, 506-16 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 81, no 3, 506-16 p.
Keyword [en]
Alcohol Drinking/physiopathology/*psychology, Animals, Body Weight/physiology, Brain/*metabolism, Eating/physiology, Enkephalin; Methionine/analogs & derivatives/metabolism, Female, Male, Maternal Deprivation, Opioid Peptides/*metabolism, Radioimmunoassay, Rats, Rats; Wistar, Research Support; Non-U.S. Gov't, Time Factors
URN: urn:nbn:se:uu:diva-75573PubMedID: 15927243OAI: oai:DiVA.org:uu-75573DiVA: diva2:103484
Available from: 2006-02-13 Created: 2006-02-13 Last updated: 2011-01-11
In thesis
1. Endogenous Opioids and Voluntary Ethanol Drinking: Consequences of Postnatal Environmental Influences in Rats
Open this publication in new window or tab >>Endogenous Opioids and Voluntary Ethanol Drinking: Consequences of Postnatal Environmental Influences in Rats
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Genetic and environmental factors interact to determine the individual vulnerability to develop ethanol dependence. The neurobiological mechanisms underlying these processes are not fully understood. Endogenous opioid peptides have been suggested to contribute. Brain opioids mediate ethanol reward and reinforcement via actions on the mesocorticolimbic dopamine system. This thesis focuses on environmental factors and investigates the impact of the early-life environment on adult voluntary ethanol consumption. The possible involvement of opioid peptides in environmental influences on adult ethanol consumption was examined using an experimental animal model.

Maternal separation with short 15 min separations (MS15) was used to simulate a safe environment whereas prolonged 360 min separations (MS360) simulated an unsafe environment. Control rats were subjected to normal animal facility rearing (AFR). The separations were performed daily from postnatal day 1 to 21. Long-term ethanol consumption was registered using a two-bottle or a four-bottle free-choice paradigm in adult male and female ethanol-preferring AA (Alko, Alcohol), ethanol-avoiding ANA (Alko, Non-Alcohol) and non-preferring Wistar rats. In addition, analyses of immunoreactive Met-enkephalin-Arg6Phe7 (MEAP), dynorphin B (DYNB) and nociceptin/orphanin FQ (N/OFQ) peptide levels were performed after maternal separation as well as after voluntary ethanol drinking.

In male rats, MS15 was related to lower ethanol consumption and these rats preferred lower concentrations, whereas MS360 was associated with an increased risk for higher consumption and/or preference for higher ethanol concentrations. Differences in basal opioid levels were observed in MS15 and MS360 rats. Furthermore, the ethanol-induced effects on opioid peptides in adults were dependent on the early environment. Female rats, on the other hand, were less affected or unaffected by maternal separation both in terms of ethanol consumption and neurobiological effects. Taken together, voluntary ethanol drinking, preference for low or high ethanol concentrations and opioid peptides in brain areas related to reward and reinforcement, motivation and stress were influenced by postnatal maternal separation in a sex dependent manner. The early environment thus had profound impact on the adult brain and the individual propensity for high ethanol drinking. A deranged endogenous opioid system contributed to these effects and may act as a mediator for long-term environmental influence on voluntary ethanol consumption.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 80 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 51
Pharmaceutical pharmacology, Maternal separation, Maternal deprivation, Handling, Isolation, Alcohol, Two-bottle model, Four-bottle model, MEAP, Dynorphin B, Nociceptin/orphanin FQ, Radioimmunoassay, Farmaceutisk farmakologi
urn:nbn:se:uu:diva-7776 (URN)978-91-554-6843-9 (ISBN)
Public defence
2007-04-20, Lecture hall B41, BMC, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2007-03-30 Created: 2007-03-30 Last updated: 2009-06-02Bibliographically approved

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