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Epidemiological and neurobiological evidence for misuse of anabolic-androgenic steroids
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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. , p. 98
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 276
Keyword [en]
Pharmaceutical biosciences
Keyword [sv]
Farmaceutisk biovetenskap
National Category
Pharmaceutical Sciences
Research subject
Biological Research on Drug Dependence
Identifiers
URN: urn:nbn:se:uu:diva-2567ISBN: 91-554-5378-3 (print)OAI: oai:DiVA.org:uu-2567DiVA, id: diva2:161909
Public defence
2002-09-27, B41, Uppsala, 09:15
Opponent
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Doping among high school students in Uppsala, Sweden: A presentation of the attitudes, distribution, side effects, and extent of use
Open this publication in new window or tab >>Doping among high school students in Uppsala, Sweden: A presentation of the attitudes, distribution, side effects, and extent of use
1998 (English)In: Scandinavian journal of social medicine. Supplementum, ISSN 0301-7311, Vol. 26, no 1, p. 71-74Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to determine the extent of doping drug use among adolescents in Uppsala, Sweden, and to analyse the main reasons for the use. An anonymous multiple-choice questionnaire was distributed among pupils in the first and the third grades at high school; 2,742 pupils participated in the study. The results showed that 2.7% of the male and 0.4% of the female adolescents had used doping drugs at some time in their life. However, knowledge of how to get doping drugs far exceeded use. The main reasons for using doping drugs were to improve appearance and to enhance performance in sports. Some boys self-reported side effects of AAS. Despite the still predominantly negative attitude toward doping prevention programs have to be taken.

Keyword
anabolic androgenic steroids, doping drugs, adolescents; epidemiology, high school students; abuse
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-89949 (URN)10.1177/14034948980260010201 (DOI)9526767 (PubMedID)
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2017-12-14Bibliographically approved
2. Factors associated with adolescent use of doping agents: anabolic-androgenic steroids
Open this publication in new window or tab >>Factors associated with adolescent use of doping agents: anabolic-androgenic steroids
1999 (English)In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 94, no 4, p. 543-553Article in journal (Refereed) Published
Abstract [en]

AIMS:

The purpose was to assess the importance of risk factors such as socio-demographics, sports activities, tobacco use, alcohol consumption, use of certain psychotropic substances and violence in the use of doping agents in adolescents.

DESIGN:

Cross-sectional survey using anonymous closed response questionnaire.

SETTING:

Eight senior high schools in Uppsala, Sweden.

PARTICIPANTS:

A total of 2742 senior high school students; 1592 were in their first year (aged 16-17 years) and 1150 in their third (aged 18-19 years).

FINDINGS:

Multiple logistic regression analyses revealed that strength training, tobacco use, heavy alcohol consumption, truancy at least once a week and living alone were significantly independently associated in the use of doping agents. Further, the study showed that use of cannabis oil, LSD, amphetamine and opioids were related specifically to anabolic-androgenic steroid use.

CONCLUSIONS:

Use of doping agents probably involves more than a desire to enhance appearance or sports performance and appears to have much in common with use of alcohol, tobacco and psychotropic drugs.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-89950 (URN)10.1046/j.1360-0443.1999.9445439.x (DOI)10605850 (PubMedID)
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2017-12-14Bibliographically approved
3. Adolescent use of anabolic-androgenic steroids and relations to self-reports of social, personality and health aspects
Open this publication in new window or tab >>Adolescent use of anabolic-androgenic steroids and relations to self-reports of social, personality and health aspects
2001 (English)In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 11, no 3, p. 322-328Article in journal (Refereed) Published
Abstract [en]

Background: Over the last decade adolescent males have been shown to use anabolic-androgenic steroids (AAS) in order to improve their sports performance and appearance, as well as in combination with alcohol and psychotropic drugs. However, the risk profile of AAS use is still not well understood. This study analysed the importance of social, personality and health factors for the use of AAS. Methods: More than 2,700 senior high school students in Uppsala, Sweden, filled out an anonymous closed-response questionnaire. Results: The findings from multiple logistic regression analyses of adolescent males (n=1,353) showed that immigrant status, average/low self-esteem, average/low perceived school achievement and use of prescription tranquillisers/sedatives had independent significant associations with the use of AAS after controlling for age and previously known factors such as strength training, truancy and heavy alcohol consumption. Conclusion: The characteristics of AAS users extend beyond activities such as strength training and multiple drug use to include social, personality and health aspects.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-89951 (URN)10.1093/eurpub/11.3.322 (DOI)
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2017-12-14Bibliographically approved
4. The anabolic-androgenic steroid nandrolone decanoate affects the density of dopamine receptors in the male rat brain
Open this publication in new window or tab >>The anabolic-androgenic steroid nandrolone decanoate affects the density of dopamine receptors in the male rat brain
Show others...
2001 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 13, no 2, p. 291-296Article in journal (Refereed) Published
Abstract [en]

In recent years a male group of anabolic-androgenic steroid misusers has been identified to share socio-demographic and personality related background factors with misusers of psychotropic substances, as well as being involved in habits of multiple drug use. The present study aimed to assess whether anabolic-androgenic steroids (AAS) would affect the density of the dopamine receptors in areas implicated in reward and behaviour in the male rat brain. The effects of 2 weeks of treatment with i.m. injections of nandrolone decanoate (15 mg/kg/day) on the expression of the D(1)-like and D(2)-like receptors were evaluated by autoradiography. Specific binding of D(1)-like receptors was significantly down regulated in the caudate putamen, the nucleus accumbens core and shell. D(2)-like receptor densities were down regulated in the nucleus accumbens shell, but up regulated in the caudate putamen, the nucleus accumbens core and the ventral tegmental area. These results are compatible with nandrolone induced neuroadaptive alterations in dopamine circuits associated with motor functions and behavioural paradigms known to be affected following AAS misuse.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-89952 (URN)10.1046/j.0953-816X.2000.01402.x (DOI)11168533 (PubMedID)
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2017-12-14Bibliographically approved
5. Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography
Open this publication in new window or tab >>Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography
Show others...
2002 (English)In: Progress in Neuro-psychopharmacology and Biological Psychiatry, ISSN 0278-5846, E-ISSN 1878-4216, Vol. 26, no 7-8, p. 1303-1308Article in journal (Refereed) Published
Abstract [en]

Anabolic-androgenic steroids (AAS) have recently been shown to induce neurochemical alterations in areas of the male rat CNS related to behavioural changes that have been observed among AAS misusers. In the present study, positron emission tomography (PET) is suggested as a suitable in vivo method in order to visualize the density of the dopamine transporter ([11C]-FE-beta-CIT) as well as the dopamine D1-like ([11C]-(+)-SCH23390) and the D2-like receptors ([11C]-raclopride) in the male rat brain. Chronic treatment with the AAS nandrolone decanoate (15 mg/kg/day for 14 days) caused an up-regulation of the binding potential of the dopamine transporter in the striatum.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-89953 (URN)10.1016/S0278-5846(02)00293-2 (DOI)12502017 (PubMedID)
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2017-12-14Bibliographically approved
6. Chronic administration with nandrolone decanoate induces alterations in the gene-transcript expression of dopamine D1- and D2-receptors in the rat brain
Open this publication in new window or tab >>Chronic administration with nandrolone decanoate induces alterations in the gene-transcript expression of dopamine D1- and D2-receptors in the rat brain
2000 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 979, no 1-2, p. 37-42Article 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-89954 (URN)10.1016/S0006-8993(03)02843-9 (DOI)12850568 (PubMedID)
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2017-12-14Bibliographically approved
7. The anabolic-androgenic steroid nandrolone induces alterations in the density of serotonergic 5HT1B and 5HT2 receptors in the male rat brain
Open this publication in new window or tab >>The anabolic-androgenic steroid nandrolone induces alterations in the density of serotonergic 5HT1B and 5HT2 receptors in the male rat brain
2003 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 119, no 1, p. 113-120Article 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-89955 (URN)10.1016/S0306-4522(03)00120-9 (DOI)12763073 (PubMedID)
Available from: 2002-09-04 Created: 2002-09-04 Last updated: 2017-12-14Bibliographically approved

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