Chronic administration with nandrolone decanoate induces alterations in the gene-transcript content of dopamine D(1)- and D(2)-receptors in the rat brain.
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.
Kindlundh
Anna M S
AM
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, S-751-24, Uppsala, Sweden. anna.kindlundh@farmbio.uu.se
Lindblom
Jonas
J
Nyberg
Fred
F
D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D017403:In Situ Hybridization; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077603:Nandrolone Decanoate; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000235:genetics
D045930:Anabolic Agents; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D009277:Nandrolone; D000077603:Nandrolone Decanoate