Effect of a peripheral and a central acting opioid antagonist on the testicular response to stress in rats.
The possible involvement of opioid receptors in mediating the inhibitory effects of immobilization stress on testicular steroidogenesis was determined in adult male rats. Unstressed controls and animals exposed to 3 h of immobilization stress were injected subcutaneously with either vehicle or 1 or 10 mg/kg body weight (BW) of naloxone or naltrexone methobromide (NMB; an opioid receptor antagonist that does not cross the blood-brain barrier) at the beginning of and at 1.5 h of the stress period. Animals were sacrificed at 2 h (30 min after the second injection of antagonist) or 3 h (90 min after the second injection of antagonist) of stress. Plasma LH was not affected by stress, but 30 min after naloxone (1 or 10 mg/kg BW) injection, LH was elevated in both control and stressed rats above levels in vehicle-injected animals. By 90 min after naloxone injection, plasma LH had declined to levels comparable to those in vehicle-injected animals. NMB had no effect on plasma LH concentrations in either control or stressed rats. Three hours of stress reduced plasma testosterone (T) levels by 60% in vehicle-injected animals. This effect of stress on plasma T levels was antagonized by the 10 mg/kg BW dose of naloxone and 1 or 10 mg/kg BW of NMB. The ability of naloxone to reverse the effect of stress on plasma T levels was likely related to its ability to stimulate LH secretion, but NMB normalized plasma T values in stressed animals without altering plasma LH concentrations. Only the highest dose of NMB increased plasma T levels in unstressed control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Akinbami
M A
MA
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310-1495.
Taylor
M F
MF
Collins
D C
DC
Mann
D R
DR
D000446:Aldehyde-Lyases / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007103:Immobilization; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009270:Naloxone; D013739:Testosterone; D009271:Naltrexone; D007986:Luteinizing Hormone; D003577:Cytochrome P-450 Enzyme System; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases; D003345:Corticosterone