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The anabolic-androgenic steroid nandrolone induces alterations in the density of serotonergic 5HT1B and 5HT2 receptors in the male 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 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.
2003 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 119, no 1, 113-120 p.Article in journal (Refereed) Published
Abstract [en]

Anabolic-androgenic steroids (AAS) are partly misused by males in order to become brave and intoxicated and these agents are highly associated with psychosis, disinhibition, aggression and acts of violence. Since such behavioral states have been related to an imbalanced serotonergic system and the involvement of the serotonergic 5HT(1B) and the 5HT(2) receptors, it was important to discern the impact of AAS on these receptors. The objective of our study was to investigate the effects of 2 weeks of treatment with the AAS nandrolone decanoate at three different doses (1, 5, 15 mg/kg/day) on the total specific binding of the radioligands [(125)I]-(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (5HT(2) receptors) by autoradiography. All doses caused a significant down-regulation of the 5HT(1B) receptor density in the hippocampal CA(1) and in the medial globus pallidus and a significant up-regulation of the 5HT(2) receptor density in the nucleus accumbens shell. Alterations in receptor density were also observed in the lateral globus pallidus, ventromedial hypothalamus, the amygdala and in the intermediate layers of various cortex regions. In conclusion, serotonergic 5HT(1B) or 5HT(2) receptors are likely to play important roles in mediating observed emotional states and behavioral changes among AAS abusers.

Place, publisher, year, edition, pages
2003. Vol. 119, no 1, 113-120 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-89955DOI: 10.1016/S0306-4522(03)00120-9PubMedID: 12763073OAI: oai:DiVA.org:uu-89955DiVA: diva2:161908
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.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 276
Keyword
Pharmaceutical biosciences, Farmaceutisk biovetenskap
National Category
Pharmaceutical Sciences
Research subject
Biological Research on Drug Dependence
Identifiers
urn:nbn:se:uu:diva-2567 (URN)91-554-5378-3 (ISBN)
Public defence
2002-09-27, B41, Uppsala, 09:15
Opponent
Available from: 2002-09-04 Created: 2002-09-04Bibliographically approved

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Kindlundh, Anna MSLindblom, JonasBergström, LenaNyberg, Fred

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