In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure.
In the present study, the effects of acute and chronic morphine exposure on testosterone concentrations in the central nervous system (CNS) and serum were investigated in rats. Acute morphine administration (5 mg/kg, s.c.) reduced significantly testosterone levels in serum and spinal cord but not in the brain. Following chronic morphine administration (orally for 21 days), the brain testosterone was also significantly reduced as well as serum and spinal cord. Since, the decrease in testosterone levels following morphine exposure was more obvious in the CNS than serum, we suggested that it cannot be caused by only a direct decline in testosterone levels in periphery, and an increased local metabolism of testosterone in the CNS might be attributed in these effects. This hypothesis was supported with the findings that pretreatment with finasteride, a 5alpha-reductase inhibitor (5 mg/kg, s.c.) blocked testosterone elimination from the CNS following morphine exposure. Moreover, the serum concentration of 5alpha-reduced metabolites of testosterone, dihydrotestosterone and 3alpha-diol glucuronide was increased significantly following chronic morphine exposure, but not after co-treatment with finasteride. These results suggest that morphine exposure increase the CNS activity of 5alpha-reductase, which is an important metabolizing enzyme for testosterone.
Amini
Hossein
H
Department of Pharmacology, Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran.
Ahmadiani
Abolhassan
A
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000201:enzymology*; D013196:Dihydrotestosterone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018120:Finasteride / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D017933:Peripheral Nervous System / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D009294:Narcotics; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride; D009020:Morphine; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase