uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Time-dependent alterations in ethanol intake in male wistar rats exposed to short and prolonged daily maternal separation in a 4-bottle free-choice paradigm
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Neuropharmacology, Addiction & Behaviour)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Neuropharmacology, Addiction & Behaviour)
2006 (English)In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 30, no 12, 2008-2016 p.Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies have shown that maternal separation can be used in animal studies of early environmental influence on adult ethanol intake. These studies have shown that short daily separations result in low ethanol intake, whereas prolonged separations relate to an enhanced risk for a high ethanol intake. The aim of the present study was to further examine the long-term effects of early-life events on ethanol intake.

Methods: Rat pups were exposed to 15 minutes (MS15) or 360 minutes (MS360) of daily maternal separation during postnatal days 1 to 21 or kept under normal animal facility rearing (AFR) conditions. In adulthood, male rats were given free access to 5, 10, and 20% ethanol, in addition to water, in a 4-bottle-choice paradigm.

Results: No differences in total ethanol intake or preference between the 3 experimental groups were found. The 54-day drinking period was divided into acquisition, stabilization, and maintenance phases for analysis of time and group differences. The MS15 rats increased ethanol intake over time; they mostly consumed 5% ethanol and had a low intake of 20% ethanol throughout the experiment. MS360 rats increased ethanol intake, changed preference from 5% to 20% ethanol, and had a higher increase in intake of 20% ethanol over time. The ethanol intake and preference in the AFR rats were more similar to that of the MS360 rats.

Conclusions: Time-dependent changes were observed in the preferred choice of low versus high ethanol concentrations in MS15 and MS360 rats. The results support previous findings suggesting that MS15 can be used as a model for environmental protective factors and that MS360 represents a risk environment for acquisition of a high adult ethanol intake.

Place, publisher, year, edition, pages
2006. Vol. 30, no 12, 2008-2016 p.
Keyword [en]
handling, maternal deprivation, early-life environment, alcohol, voluntary intake
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-22951DOI: 10.1111/j.1530-0277.2006.00247.xISI: 000242041800008PubMedID: 17117966OAI: oai:DiVA.org:uu-22951DiVA: diva2:50724
Available from: 2007-01-23 Created: 2007-01-23 Last updated: 2011-05-13Bibliographically approved
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

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Nylander, Ingrid
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Alcoholism: Clinical and Experimental Research
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 162 hits
ReferencesLink to record
Permanent link

Direct link