Effect of N ω ‐nitro‐ l ‐arginine methyl ester, a nitric oxide synthesis inhibitor, on stress‐ and morphine‐induced prolactin release in male rats

The effect of the nitric oxide synthesis inhibitor N ω ‐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. 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.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. 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. 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.British Journal of Pharmacology (1997) 120 , 268–272; doi: 10.1038/sj.bjp.0700899