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The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of dopaminergic but not serotonergic receptors
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, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2008 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1240, 221-228 p.Article in journal (Refereed) Published
Abstract [en]

The abuse of anabolic androgenic steroids (AASs) at supratherapeutic doses is a problem not only in the world of sports, but also among non-athletes using AASs to improve physical appearance and to become more bold and courageous. Investigations of the possible neurochemical effects of AAS have focused partially on the monoaminergic systems, which are involved in aggressive behaviours and the development of drug dependence. In the present study, we administered nandrolone decanoate (3 or 15 mg/kg/day for 14 days) and measured mRNA expression of dopaminergic and serotonergic receptors, transporters and enzymes in the male rat brain using quantitative real-time polymerase chain reaction. Expression of the dopamine D1-receptor transcript was elevated in the amygdala and decreased in the hippocampus while the transcript level of the dopamine D4-receptor was increased in the nucleus accumbens. No changes in transcriptional levels were detected among the serotonin-related genes examined in this study. The altered mRNA expression of the dopamine receptors may contribute to some of the behavioural changes often reported in AAS abusers of increased impulsivity, aggression and drug-seeking.

Place, publisher, year, edition, pages
2008. Vol. 1240, 221-228 p.
Keyword [en]
Anabolic androgenic steroid, Dopamine receptor, Nandrolone decanoate, Serotonin receptor, Quantitative real-time PCR
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97443DOI: 10.1016/j.brainres.2008.09.003ISI: 000261415600025PubMedID: 18809391OAI: oai:DiVA.org:uu-97443DiVA: diva2:172397
Available from: 2008-09-05 Created: 2008-09-05 Last updated: 2011-12-02Bibliographically approved
In thesis
1. Anabolic androgenic steroids and central monoaminergic systems: Supratherapeutic doses of nandrolone decanoate affect dopamine and serotonin
Open this publication in new window or tab >>Anabolic androgenic steroids and central monoaminergic systems: Supratherapeutic doses of nandrolone decanoate affect dopamine and serotonin
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Supratherapeutic doses of anabolic androgenic steroids (AASs) are administered, not only as performance-enhancing drugs in the world of sports, but also in order to modify behaviour. AAS abusers are at risk of developing serious physical and psychological side effects such as dependence and aggressive behaviour. The aim of this thesis was to investigate the impact of supratherapeutic doses of nandrolone decanoate after subchronic administration on dopamine and serotonin pathways involved in drug dependence and aggression, in the male rat brain.

Adult male Sprague-Dawley rats received intramuscular injections of nandrolone decanoate (3 or 15 mg/kg) or vehicle once daily for 14 days. Nandrolone decanoate pre-exposure abolished the effect of amphetamine on the 3,4-dihydroxyphenylacetic acid (DOPAC) tissue level in the hypothalamus and on the DOPAC/dopamine ratio in the hypothalamus and the hippocampus. A significant decrease of the basal extracellular DOPAC and homovanillic acid (HVA) levels could be detected in the nucleus accumbens, which remained low during the first hour following the amphetamine challenge. Nandrolone decanoate significantly reduced the activity of both monoamine oxidase A and B (MAO-A and -B) in the caudate putamen and amygdala. The gene transcript levels of MAO-B, and the dopamine D1 and D4 receptors were altered in limbic regions. No changes in transcriptional levels could be detected among the serotonin receptor genes examined. However, the density of the serotonin transporter protein was elevated in a range of aggression-related brain regions.

Taken together, subchronic administration of nandrolone decanoate causes dopaminergic and serotonergic dysregulations in distinct brain regions. These areas of the brain are involved in the development of drug dependence and expression of impulsive and aggressive behaviours. These results may contribute to explain some of the behavioural changes often reported in AAS abusers, such as polydrug use and impaired impulse control.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 77
Keyword
Pharmacology, anabolic androgenic steroids, nandrolone decanoate, dopamine, serotonin, rat, central nervous system
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-9208 (URN)978-91-554-7259-7 (ISBN)
Public defence
2008-09-26, B22, BMC, Husargatan, Uppsala, 13:00
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Available from: 2008-09-05 Created: 2008-09-05Bibliographically approved

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