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Chronic administration with nandrolone decanoate induces alterations in the gene-transcript expression of dopamine D1- and D2-receptors in the rat brain
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 Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2000 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 979, no 1-2, 37-42 p.Article in journal (Refereed) Published
Abstract [en]

Some adolescent and young males are engaged in misuse of anabolic-androgenic steroids (AASs) in connection with multiple drug use, in order to become intoxicated and brave, apart from currently known motives connected to sports performance and physical appearance. Recent studies suggest that alterations in neurobiological circuits implicated in the regulation of reward-related learning, aggression and motoric behavior underlie the behavioral changes associated with AAS misuse. We have previously shown that AASs induce alterations in dopamine receptor densities. The aim of the present study was to investigate if these effects could be attributed to altered mRNA content for tyrosine hydroxylase, L-amino acid decarboxylase, dopamine D(1)- and dopamine D(2)-receptor as measured by in situ hybridisation. Male Sprague-Dawley rats were subjected to 2 weeks of treatment with daily intramuscular injections of the AAS nandrolone decanoate at three different doses (1, 5 and 15 mg/kg/day). Results of the in situ hybridization showed that the mRNA content of the dopamine D(1)-receptor subtype was significantly reduced at all doses in the caudate putamen and at the highest doses in the nucleus accumbens shell. The mRNA expression of the dopamine D(2)-receptor was significantly increased at the two lowest doses in the caudate putamen and the nucleus accumbens shell. In conclusion, nandrolone has been shown to affect the expression of gene transcripts of dopaminergic receptors possibly implicated in underlying mechanisms of reward-related behavioral changes among AAS misusers.

Place, publisher, year, edition, pages
2000. Vol. 979, no 1-2, 37-42 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89954DOI: 10.1016/S0006-8993(03)02843-9PubMedID: 12850568OAI: oai:DiVA.org:uu-89954DiVA: diva2:161907
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2013-09-19Bibliographically approved
In thesis
1. Epidemiological and neurobiological evidence for misuse of anabolic-androgenic steroids
Open this publication in new window or tab >>Epidemiological and neurobiological evidence for misuse of anabolic-androgenic steroids
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Misuse of anabolic-androgenic steroids (AAS), is attributed to elite athletes and body builders. The attentive involvement of AAS in acts of violence seen in society has raised interest to evaluate the importance of social, psychological and neurobiological mechanisms that underlie the psychiatric states associated with onset of controlled misuse, its maintenance, and via abuse its transition to addiction. The objective of this thesis is to examine whether misuse of AAS shares mechanisms with epidemiological and neurobiological models of psychotropic substances.

Epidemiological studies through a survey conducted in Uppsala, Sweden, suggest that misuse of doping agents, specifically AAS, has extended also to include adolescent males taking these agents in order to improve muscle mass, enhance sports performance, become intoxicated, braver, and because it is fun to try. Intake of AAS is in a subgroup highly connected to misuse of psychotropic substances. The adolescent AAS profile is highlighted in a multivariate model positing the factors high immigrant status, perceived average/bad school achievement, truancy, average/low self-esteem, strength training, heavy alcohol consumption and use of prescription tranquillisers to be independently associated with lifetime misuse.

Neurobiological studies indicate that chronic treatment with supra-therapeutic doses of the AAS nandrolone, significantly affects dopamine receptor density in the male rat brain and the corresponding gene transcripts in the mesocorticolimbic and nigrostriatal dopamine systems, in brain areas of importance for hedonia, reward-related learning, incentives and motoric behaviours. Identical treatment regimen affects the density of serotonin receptors in regions regulating anxiety, aggression, cognitive functions, impulsivity and its associated loss of inhibitory control. These alterations may reflect aversive conditions that could be linked to severe alleostatic states of addiction following chronic continuous "binge" intoxications of addictive drugs.

Thus, the AAS profile of misuse shares similarities with mechanisms of psychotropic substances regarding psychological and social models of onset and maintenance and with respect to AAS-induced neurobiological changes in the brain. This trend is alarming, strengthening the need of prevention and treatment programs targeting the specific subgroups of misusers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 98 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 276
Pharmaceutical biosciences, Farmaceutisk biovetenskap
National Category
Pharmaceutical Sciences
Research subject
Biological Research on Drug Dependence
urn:nbn:se:uu:diva-2567 (URN)91-554-5378-3 (ISBN)
Public defence
2002-09-27, B41, Uppsala, 09:15
Available from: 2002-09-04 Created: 2002-09-04Bibliographically approved

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