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The effect on opioid peptides in the rat brain, after chronic treatment with the anabolic androgenic steroid, nandrolone decanoate
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.
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.
2000 (English)In: Brain Research Bulletin, ISSN 0361-9230, E-ISSN 1873-2747, Vol. 51, no 5, 413-418 p.Article in journal (Refereed) Published
Abstract [en]

In recent years, an increase in abuse of anabolic androgenic steroids (AAS) has been seen among individuals not directly connected to sports. Clinical evidence suggests that abuse of these steroids may result in profound changes in personality, expressed by depressive symptoms, irritability and increased aggression. It is still unknown whether these alterations are related to changes in any particular transmitter system or whether they are persistent or reversible. In this study we focused on AAS effect on the endogenous dynorphin and enkephalin system in the brain. Male rats were given intramuscular injections of the AAS nandrolone decanoate (15 mg/kg), once daily for 2 weeks. The levels of the opioid peptide immunoreactivities (ir) were assessed by radioimmunoassay in two groups immediately after the treatment and in two other groups after additional 3 weeks without any drug treatment (recovery period). The result indicates that chronic AAS treatment increased the activity in the dynorphin B- and Met-enkephalin-Arg6Phe7-ir in the hypothalamus, striatum and periaqueductal gray (PAG) compared to controls. In addition, the steroid induced an imbalance between the dynorphin and the enkephalin opioid system in the nucleus accumbens, hypothalamus and PAG. This imbalance remained after the recovery period. Since increased peptide activity was found in brain regions regulating emotions, dependence, defensive reactions and aggression, it was suggested that the actual endogenous opioid systems are involved in previously reported AAS-induced changes in these behaviours.

Place, publisher, year, edition, pages
2000. Vol. 51, no 5, 413-418 p.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92902DOI: 10.1016/S0361-9230(99)00263-4OAI: oai:DiVA.org:uu-92902DiVA: diva2:166218
Available from: 2005-04-18 Created: 2005-04-18 Last updated: 2012-10-08Bibliographically approved
In thesis
1. Anabolic Androgenic Steroids: Effects on Neuropeptide Systems in the Rat Brain
Open this publication in new window or tab >>Anabolic Androgenic Steroids: Effects on Neuropeptide Systems in the Rat Brain
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Anabolic-androgenic steroids (AAS) have been used in clinics for decades. The misuse of AAS has previously been attributed merely to sport athletes, taking AAS with intentions to increase muscle mass, enhance physical performance and to improve results in competitions. Today, the misuse of AAS has spread to adolescents and young adults not connected to sports. Alarmingly, many reports are pointing at severe psychiatric adverse effects among AAS abusers, which include mood swings, mania, anxiety, depression and aggression. Numerous examples of severe and often unprovoked violence and brutal crimes have been connected to AAS abuse and there is a strong need for a better understanding of the underlying biochemical events that might account for the adverse behaviors induced by AAS. The general aim of this thesis was to study the effect of chronic AAS administration on neuropeptide circuits in the rat brain associated with the regulation of rewarding effects, memory, anxiety, depression and aggression, using nandrolone decanoate as a prototype AAS.

Results demonstrated that daily administration of AAS to rats in doses comparable to those taken by AAS abusers, in certain brain structures significantly affected, a) the levels of the opioid peptides dynorphin B and Met-enkephalin-Arg6Phe7, b) the levels of the tachykinin substance P (SP), c) the density of the SP neurokinin 1 (NK1) receptor, d) the level of the SP metabolite SP1-7 that frequently exerts opposite effects to SP, e) the SP1-7 generating enzyme substance P endopeptidase (SPE) and finally, f) the levels of the neuropeptide calcitonin gene-related peptide (CGRP) often co-localized with SP. The alterations seen in the levels and activities of these neurochemical components are in many aspects compatible with behaviors typified among AAS abusers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 60 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 9
Keyword
Biological research on drug dependence, Anabolic androgenic steroids, Nandrolone decanoate, Substance P, NK1 receptor, Substance P(1-7), Endopeptidase, Opioids, Calcitonin gene-related peptide, Radioimmunoassay, Autoradiography, Central nervous system, Rats, Biologisk beroendeforskning
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-5745 (URN)91-554-6214-6 (ISBN)
Public defence
2005-05-11, B41, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2005-04-18 Created: 2005-04-18Bibliographically approved

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Hallberg, MathiasKindlundh, AnnaNyberg, Fred

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