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Long-term effects of maternal separation on ethanol intake and brain opioid and dopamine receptors in male Wistar rats.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2003 (English)In: Neuroscience, no 121, 787-799 p.Article in journal (Other (popular scientific, debate etc.)) Published
Place, publisher, year, edition, pages
2003. no 121, 787-799 p.
Identifiers
URN: urn:nbn:se:uu:diva-71843OAI: oai:DiVA.org:uu-71843DiVA: diva2:99754
Available from: 2005-05-13 Created: 2005-05-13 Last updated: 2011-01-13
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
2. Maternal Separation in Rats: An Experimental Model for Long-Term Effects of Early Life Experiences on Neurochemistry, Voluntary Ethanol Intake and Exploration and Risk Assessment Behavior
Open this publication in new window or tab >>Maternal Separation in Rats: An Experimental Model for Long-Term Effects of Early Life Experiences on Neurochemistry, Voluntary Ethanol Intake and Exploration and Risk Assessment Behavior
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The period of early life is important for the development of individual brain function and behavior. Human studies have shown altered vulnerability to develop psychopathology and/or excessive drug intake, possibly leading to dependence, as a consequence of early life experiences. In the present thesis, maternal separation (MS), an experimental model for studies of early environmental influences, was used to investigate long-term effects on neurochemistry, voluntary ethanol intake and exploration and risk assessment behavior in rats. Rat pups were assigned to one of three different rearing conditions: daily 15 min (MS15) or 360 min (MS360) of MS and normal animal facility rearing (AFR) during the first three weeks of life. Measurements of adult endogenous opioid peptide levels, opioid- and dopamine receptor density revealed minor MS-induced effects on the opioid system whereas interesting alterations were found in dopamine receptor density. Long-term effects on voluntary ethanol intake showed distinct MS-induced alterations in male Wistar and ethanol-preferring AA (Alko, Alcohol) rats. Female Wistar rats were unaffected, indicating sex differences in the effects of MS on ethanol intake. Male MS15 rats generally had a slower acquisition phase and a low subsequent ethanol intake whereas male MS360 rats had a high ethanol intake. MS15 is therefore suggested to protect against a high voluntary ethanol intake in male rats whereas MS360 may serve as a risk factor. The recently established concentric square field test indicated alterations in risk assessment as well as an increased exploratory drive and somewhat higher risk-taking behavior in adult MS360 rats, while minor effects were seen in MS15 rats. Altogether, these results demonstrate that environmental influences during the period of early life can have long-term effects on neurochemistry and behavior. Of special interest is the finding that MS altered the inherited high ethanol intake in adult ethanol-preferring AA rats.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 81 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 313
Keyword
Pharmaceutical pharmacology, Handling, Maternal Deprivation, Environment, Opioids, Dopamine, Alcohol, Stress, Concentric Square Field, Open Field, Elevated Plus-maze, Farmaceutisk farmakologi
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-4465 (URN)91-554-6009-7 (ISBN)
Public defence
2004-09-24, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2004-09-03 Created: 2004-09-03 Last updated: 2009-06-02Bibliographically approved

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Roman, ErikaNylander, Ingrid

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