Administration of the anabolic androgenic steroid nandrolone decanoate affects substance P endopeptidase-like activity in the rat brain.
The effect of the anabolic androgenic steroid, nandrolone decanoate, on substance P endopeptidase-like activity was examined in adult male Sprague-Dawley rats. Nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) were administered by intramuscular injections during 14 days. Substance P endopeptidase, a predominantly cytosolic enzyme, generates the bioactive N-terminal fragment substance P(1-7) from the enzyme substrate substance P. Nandrolone decanoate significantly reduced the substance P endopeptidase-like activity compared to control animals in hypothalamus (43% reduction), caudate putamen (44%), substantia nigra (32%) and the ventral tegmental area (27%). It was previously reported that both hypothalamus and caudate putamen contained significantly higher levels of substance P after nandrolone administration. The higher concentration of substance P in these regions could to an extent be attributed to the reduction in substance P endopeptidase-like activity. This result elucidates the important role of peptidase activity in the regulation of the substance P transmitter system. The present study provides additional support for the hypothesis that alterations in the substance P system in certain brain areas may contribute to some of the personality changes reported in connection with AAS abuse.
Magnusson
Kristina
K
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, BMC, Box 591, 751 24 Uppsala, Sweden. Kristina.Magnusson@farmbio.uu.se
Hallberg
Mathias
M
Högberg
Anna M S Kindlundh
AM
Nyberg
Fred
F
D000679:Amygdala / Q000187:drug effects / Q000201:enzymology; D045930:Anabolic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002216:Captopril; D007273:Injections, Intramuscular; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D010446:Peptide Fragments / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*
D045930:Anabolic Agents; D010446:Peptide Fragments; D013373:Substance P; D009277:Nandrolone; D002216:Captopril; D008666:Metalloendopeptidases; C029610:substance P degrading enzyme; D000077603:Nandrolone Decanoate