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 inhibito ry 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 eit her vehicle or 1 or 10 mg/kg body weight (BW) of naloxone or naltrexon e 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 stre ss period. Animals were sacrificed at 2 h (30 min after the second inj ection of antagonist) or 3 h (90 min after the second injection of ant agonist) of stress. Plasma LH was not affected by stress, but 30 min a fter naloxone (I or 10 mg/kg BW) injection, LH was elevated in both co ntrol and stressed rats above levels in vehicle-injected animals. By 9 0 min after naloxone injection, plasma LH had declined to levels compa rable to those in vehicle-injected animals. NMB had no effect on plasm a LH concentrations in either control or stressed rats. Three hours of stress reduced plasma testosterone (T) levels by 60% in vehicle-injec ted 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 a bility of naloxone to reverse the effect of stress on plasma T levels was likely related to its ability to stimulate LH secretion, but NMB n ormalized plasma T values in stressed animals without altering plasma LH concentrations. Only the highest dose of NMB increased plasma T lev els in unstressed control animals. The activities (V(max)) of testicul ar 17 alpha-hydroxylase and 17,20-lyase were significantly reduced by 3 h of stress. K(m) values for both enzymes were unchanged in stressed rats. Both naloxone and NMB normalized the activity of both enzymes i n stressed animals, but did not alter the activity of the enzymes in u nstressed rats. These results demonstrate that NMB, a peripheral actin g opioid antagonist, counteracts the inhibitory effect of stress on pl asma T levels and on testicular activity of 17 alpha-hydroxylase and 1 7,20-lyase independent of an effect on plasma LH concentrations. The s tudy provides evidence for the involvement of peripheral opioid recept ors (perhaps testicular opioid receptors) in mediating the inhibitory effect of immobilization stress on testicular steroidogenesis. Data fr om this study also supports the hypothesis that opioids directly modul ate testicular testosterone secretion in unstressed control animals.