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Enzymatic conversion of dynorphin A in the rat brain is affected by administration of nandrolone decanoate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Biological Research on Drug Dependence.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Biological Research on Drug Dependence.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Biological Research on Drug Dependence.
2007 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 28, no 4, 851-858 p.Article in journal (Refereed) Published
Abstract [en]

The misuse of anabolic androgenic steroids (AAS) seems to produce profound effects on the central nervous system, leading to aggressive behavior and increased sensitivity to other drugs of abuse. The present study addresses the effect on the enzymatic transformation, here called dynorphin converting enzyme-like activity. The formation of the mu/delta opioid peptide receptor-preferring Leu-enkephalin-Arg6 from the kappa opioid peptide receptor-preferring dynorphin A was measured in rats treated with nandrolone decanoate. Significant variations in enzymatic transformation were observed in several brain regions. An altered receptor activation profile in these regions may be one contributory factor behind AAS-induced personality changes.

Place, publisher, year, edition, pages
2007. Vol. 28, no 4, 851-858 p.
Keyword [en]
Anabolic androgenic steroids (AAS), Nandrolone decanoate, Dynorphin converting enzyme, Rat brain, Enzyme, Dynorphin
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-10868DOI: 10.1016/j.peptides.2006.12.011ISI: 000245625900017PubMedID: 17240479OAI: oai:DiVA.org:uu-10868DiVA: diva2:38636
Available from: 2007-04-26 Created: 2007-04-26 Last updated: 2017-12-11Bibliographically approved
In thesis
1. The Impact of Nandrolone Decanoate on Neuropeptidergic Mechanisms Related to Cognition, Aggression, Reward and Dependence
Open this publication in new window or tab >>The Impact of Nandrolone Decanoate on Neuropeptidergic Mechanisms Related to Cognition, Aggression, Reward and Dependence
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The abuse of anabolic androgenic steroids (AAS) is becoming increasingly common and may result in a range of physiological as well as psychological effects such as altered behavior in terms of increased aggression, cognitive dysfunction and addictive behavior. AAS comprise testosterone and its derivatives, of which nandrolone is one of the more common. Previous studies have shown nandrolone-induced effects in male rats on peptide levels within the Substance P (SP) system and the dynorphinergic system; these effects may be linked to some of the reported behavior alterations. The studies presented in this thesis aimed to investigate the mechanisms underlying these peptide alterations and also to further investigate neuropeptidergic effects attributed to nandrolone administration. The results display significant effects on the enzymatic conversion of SP and Dynorphin A into their bioactive metabolites SP(1-7) and Leu-enkephalin-Arg6, respectively, as a result of nandrolone treatment. More profound investigations on the dynorphinergic system displayed effects on the kappa opioid receptor density in various brain regions. There was also a significant increase in the expression of the gene transcript of prodynorphin in the hippocampus, a brain region associated with cognitive processes. In addition, impaired spatial learning and memory in the Morris water maze task following nandrolone administration was encountered. The results provide further understanding regarding neuropeptidergic mechanisms underlying AAS-induced behavioral effects.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 103
Keyword
Anabolic androgenic steroids, Nandrolone decanoate, Substance P, Dynorphin A, KOP receptor, Prodynorphin, Radioimmunoassay, Autoradiography, Morris water maze, PCR, Central nervous system
National Category
Pharmacology and Toxicology
Research subject
Biological Research on Drug Dependence
Identifiers
urn:nbn:se:uu:diva-107483 (URN)978-91-554-7587-1 (ISBN)
Public defence
2009-09-25, B42, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2009-09-03 Created: 2009-08-12 Last updated: 2011-05-05Bibliographically approved

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Magnusson, KristinaHallberg, MathiasBergquist, JonasNyberg, Fred

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