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

Abstract

1 The eect of the nitric oxide synthesis inhibitor N o -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 71 ) and were given intraperitoneally one hour before blood sampling; control rats received saline. After the ®rst blood sample, rats received an initial intravenous injection of morphine (3, 6 or 12 mg kg 71 ) 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 71 , respectively) 90 min later, when tolerance had developed, while rats subjected to immobilization stress received 6 mg kg 71 morphine 90 min after onset of stress. 3 L-NAME had no eect on basal plasma PRL concentration. However, it potentiated acute morphineinduced 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 71 ) was combined with the highest dose of L-NAME pretreatment (30 mg kg 71 ), 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 eect, and some possible mechanisms are discussed.

Effect of nitric oxide on prolactin secretion and hypothalamic biogenic amine contents

“…The increase in mean levels of prolactin after L-NAME administration, found in the present study, differ from previous works from the literature showing opposite (Bonavera et al, 1994) or no effects (Aguilar et al, 1997;Chiodera et al, 1998;Matton et al, 1997;González et al, 1996) when analyzed at single point assay. The discrepancies may be attributed to the differences in the experimental approaches used in every study: route of administration of L-NAME, dose of L-NAME used, or time of the day in which the experiment was carried out.…”

“…Serotonin may have differential effects on prolactin secretion at the hypothalamic (Toumisto and Mannisto, 1985) or the hypophyseal level (Spangelo et al, 1990). Other neuroinmuno-modulators, not studied in this work, could also be changed by modifications in NO production (Aguilar et al, 1997;Chiodera et al, 1998;Duvilanski et al, 1995;Matton et al, 1997;Theas et al, 2001).…”

“…administered with N N -nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, at a dose of 10 mg/Kg in saline, 60 minutes before the beginning of the bleeding period. The doses and timing for L-NAME administration were selected according to previous data from the literature (Matton et al, 1997;Yen and Pan, 1999;Pinilla et al, 2001). One hour after the beginning of the intravenous infusion of saline, and 15 min after the administration of 300 IU of heparin, rats were continuously bled through a peristaltic pump at a flow rate of 50 AL, every 7 min.…”

Potentiation by nitric oxide synthase inhibitor and calcium channel blocker of aspartame‐induced antinociception in the mouse formalin test

“…Activation of N‐Methyl‐D‐Aspartate (NMDA) receptor leads to calcium influx [4] and release of calcium from intracellular stores [5] and increased production of nitric oxide (NO) [6]. NO is formed from L‐arginine by the calcium‐calmodulin requiring enzyme, NO synthase (NOS) under physiological conditions and exerts its actions mainly via activation of soluble guanylate cyclase [7,8]. Recently it was suggested that there is a role for NO pathway on modulation of pain [9–12] and inflammation [13,14] in animals and human [15].…”

Interactions between morphine and nitric oxide in various organs

“…L-NAME potentiated acute morphine-induced prolactin secretion and attenuated the subsequent tolerance to morphine in rats, whereas immobilization stressinduced prolactin secretion was inhibited by L-NAME, as was the subsequent tolerance to morphine [74]. Morphine subcutaneously injected to rat pups elicited increases in both adrenocorticotropic hormone (ACTH) and corticosterone secretion, these responses increasing with advancing postnatal age; naloxone, when concomitantly administered with morphine, was unable to block the morphine-induced responses, but in contrast, they were blocked by pretreatment with naloxone or L-NAME [75].…”