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Early Environmental Factors Differentially Affect Voluntary Ethanol Consumption in Adolescent and Adult Male Rats
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Neuropharmacology, Addiction & Behaviour)
2011 (English)In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 35, no 3, 506-515 p.Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies using the maternal separation (MS) model have shown that environmental factors early in life affect adult ethanol consumption. Prolonged MS is related to enhanced propensity for high adult ethanol intake when compared to short MS. Less is known about the environmental impact on adolescent ethanol intake. In this study, the aim was to compare establishment of voluntary ethanol consumption in adolescent and adult rats subjected to different rearing conditions. Methods: Wistar rat pups were separated from their mother 0 minutes (MS0), 15 minutes (MS15), or 360 minutes (MS360) daily during postnatal days (PNDs) 1 to 20. After weaning, the male rats were divided into two groups; rats were given free access to water, 5 and 20% ethanol at either PND 26 or 68. Ethanol was provided in 24-hour sessions three times per week for 5 weeks. Results: MS resulted in altered ethanol consumption patterns around the pubertal period but otherwise the rearing conditions had little impact on ethanol consumption in adolescents. In adults, the establishment of ethanol consumption was dependent on the rearing condition. The adult MS0 and MS15 rats had a stable ethanol intake, whereas the MS360 rats increased both their ethanol intake and preference over time. Conclusions: With the use of intermittent access to ethanol, new data were provided, which confirm the notion that MS360 represents a risk environment related to higher ethanol intake compared to MS15. The adolescent rats had higher ethanol intake than adult rats but the consumption was independent of rearing condition. Experiences during the first three postnatal weeks thus affect the establishment of voluntary ethanol consumption differently in adolescent and adult rats. Further studies are now warranted to examine the consequences of a combination of early environmental influence and high adolescent ethanol intake.

Place, publisher, year, edition, pages
2011. Vol. 35, no 3, 506-515 p.
Keyword [en]
Maternal Separation, Intermittent Access, Alcohol, Risk Factor, Protective Factor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-149788DOI: 10.1111/j.1530-0277.2010.01367.xISI: 000288143100014PubMedID: 21143247OAI: oai:DiVA.org:uu-149788DiVA: diva2:405605
Available from: 2011-03-23 Created: 2011-03-23 Last updated: 2017-12-11
In thesis
1. Early Environment and Adolescent Ethanol Consumption : Effects on Endogenous Opioids and Behaviour in Rats
Open this publication in new window or tab >>Early Environment and Adolescent Ethanol Consumption : Effects on Endogenous Opioids and Behaviour in Rats
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Excessive and compulsive ethanol drinking is one of the most serious public health issues. Therefore, it is vital to increase the knowledge about risks and protection for alcohol use disorders (AUD) to optimize prevention and treatment strategies. Ethanol consumption commonly initiates during adolescence when extensive neuronal maturation and development also occurs. Early exposure to ethanol is a risk factor for AUD, but the effects of adolescent drinking and the basis for the individual susceptibility to AUD are not fully understood. The interactions between genotype and environmental factors determine the individual risk for AUD and this thesis aimed to examine the environmental impact. The specific aims were to investigate 1) how early-life conditions affect adolescent voluntary ethanol drinking, behavioural profiles, endogenous opioids and response to treatment with an opioid antagonist (naltrexone), and 2) whether alterations detected in the offspring may be mediated by variations in maternal behaviour. A rodent maternal separation (MS) model was used to mimic a protective and risk-inducing early-life environment, respectively, with the use of 15 min (MS15) or 360 min (MS360) of daily MS. The main findings were 1) the MS360, but not the MS15 rats, responded to naltrexone following adolescent ethanol drinking; all adolescent rats had a high voluntary ethanol intake independent of early environmental conditions whereas in the adult groups the MS360, but not the MS15 rats, increased their ethanol intake and preference over time; adolescent ethanol exposure resulted in higher dynorphin levels in hippocampus and higher Met-enkephalin-Arg6Phe7 in the amygdala, independently of rearing conditions, 2) behavioural profiling using the multivariate concentric square field™ test showed: the young MS360 rats had increased risk assessment and risk taking behaviour compared to the young MS15 rats; the young MS15 rats increased, whereas the young MS360 rats decreased, their risk assessment and risk taking behaviour over time; differences in pup-retrieval strategies where the MS360 dams retrieved some pups into a safe area but as compared to MS15 rats they left more pups in a risk area; increased risk assessment behaviour in the MS360 dams immediately after weaning. Taken together, early-life environmental conditions alter adult but not adolescent drinking, the response to naltrexone, and behaviour in dams and offspring. Adolescent rats consumed more ethanol independent of rearing conditions and displayed increased opioid levels in brain areas related to cognition and addiction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 91 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 171
Keyword
Alcohol, intermittent ethanol access, maternal separation, multivariate concentric square field™ test, maternal behavior, ultrasonic vocalization, adolescent, neonatal handling
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Pharmacology
Identifiers
urn:nbn:se:uu:diva-198670 (URN)978-91-554-8678-5 (ISBN)
Public defence
2013-06-14, B22, BMC, Husargatan, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2013-05-24 Created: 2013-04-22 Last updated: 2014-04-23Bibliographically approved

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Daoura, LoudinNylander, Ingrid

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