Effect of N omega-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, on stress- and morphine-induced prolactin release in male rats.
1. The effect of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was investigated on stress- and morphine-induced prolactin (PRL) secretion in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Three doses of L-NAME were tested (1, 10 and 30 mg kg-1) and were given intraperitoneally one hour before blood sampling; control rats received saline. After the first blood sample, rats received an initial intravenous injection of morphine (3, 6 or 12 mg kg-1) or were subjected to immobilization stress. In the case of a morphine administration, rats received a second dose of morphine (3, 6 or 6 mg kg-1, respectively) 90 min later, when tolerance had developed, while rats subjected to immobilization stress received 6 mg kg-1 morphine 90 min after onset of stress. 3. L-NAME had no effect on basal plasma PRL concentration. However, it potentiated acute morphine-induced PRL secretion and attenuated the subsequent tolerance in a dose-dependent way. Immobilization stress-induced PRL secretion was inhibited dose-dependently by L-NAME, as was its subsequent tolerance to morphine; however, in this case, in a reversed dose-dependent way. 4. When the highest dose of morphine (12 mg kg-1) was combined with the highest dose of L-NAME pretreatment (30 mg kg-1), all rats showed a dramatic potentiation of the morphine-induced PRL rise compared to controls. Moreover, all of these rats died within 90 min after the administration of morphine. 5. These results show that NO plays a role in the acute opioid action on PRL release during stress as well as in the development of tolerance to the opioid effect, and some possible mechanisms are discussed.
Matton
A
A
Department of Pharmacology, Faculty of Medicine, Vrije Universiteit Brussel, Belgium.
Bollengier
F
F
Finné
E
E
Vanhaelst
L
L
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009294:Narcotics; D009020:Morphine; D011388:Prolactin; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester