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Neonatal handling in rats induces long-term effects on dynorphin peptides
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Pharmacology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Pharmacology)
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1999 (English)In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 33, no 6, 468-474 p.Article in journal (Refereed) Published
Abstract [en]

The effects of neonatal handling on the opioid dynorphin peptides in the brain and pituitary gland of Sprague-Dawley rats were investigated. Ten weeks after the neonatal handling, handled rats had higher tissue levels of dynorphin A and B in the hypothalamus, pituitary gland and striatum and slightly higher dynorphin B levels in the hippocampus, medulla oblongata and midbrain as compared with non-handled controls. The results indicate a persistent upregulation of the dynorphin system in certain brain areas after neonatal handling, which could contribute to the behavioural changes in these rats observed later in life. Observation in the open field and the elevated plus-maze tests confirmed behavioural effects of neonatal handling, i.e. showing that handled rats exhibit attenuated fearfulness in novel environments as compared with non-handled rats.

Place, publisher, year, edition, pages
1999. Vol. 33, no 6, 468-474 p.
National Category
Pharmaceutical Sciences Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-50738DOI: 10.1054/npep.1999.0764ISI: 000085477700005PubMedID: 10657526OAI: oai:DiVA.org:uu-50738DiVA: diva2:78647
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-05Bibliographically 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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