title: Altered extracellular levels of DOPAC and HVA in the rat nucleus accumbens shell in response to sub-chronic nandrolone administration and a subsequent amphetamine challenge.
abstract: Associated with acts of violence and polydrug use, abuse of anabolic androgenic steroids (AAS) is an increasing problem in society. The aim of the present study was to elucidate whether sub-chronic treatment with the AAS nandrolone decanoate affects dopamine release and dopamine metabolism in the rat nucleus accumbens shell, before and after an amphetamine challenge. Male Sprague-Dawley rats received daily i.m. injections of nandrolone decanoate (15 mg/kg) or vehicle for 14 days. On day 15, the animals were anaesthetized and a microdialysis probe was implanted into the nucleus accumbens shell. Extracellular fluid was collected 1h before and 3h after a single amphetamine injection (5 mg/kg). The samples were then analyzed regarding the content of dopamine, and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using HPLC with electrochemical detection. Two weeks of nandrolone decanoate administration caused a significant decrease of the basal DOPAC and HVA levels, which remained low during the first hour following the amphetamine challenge. Dopamine levels did not differ significantly between groups, neither after the nandrolone pre-treatment nor the amphetamine challenge. In conclusion, these novel findings indicate that AAS alter the metabolism of dopamine in a brain region involved in the development of drug dependence.
authors.affiliation: Department of Pharmaceutical Biosciences, Division of Pharmaceutical Pharmacology, Uppsala University, Box 591 Biomedical Centre, SE-751 24 Uppsala, Sweden. carolina.birgner@farmbio.uu.se
authors.forename: Carolina
authors.initials: C
authors.lastname: Birgner
authors.forename: Anna M S
authors.initials: AM
authors.lastname: Kindlundh-Högberg
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.forename: Lena
authors.initials: L
authors.lastname: Bergström
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology*; D045930:Anabolic Agents / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009277:Nandrolone / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D045930:Anabolic Agents; D018765:Dopamine Uptake Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D009277:Nandrolone; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid