Pure narcotic antagonists such as naloxone and naltrexone have consistently been shown to attenuate drinking in the rat after periods of water deprivation. One objective of this study was to extend observations to a primate species, the squirrel monkey. Whereas naloxone and naltrexone have a greater relative affinity for opiate receptors preferentially binding morphine and other opiate alkaloids than for those with high affinity for the endogenous opioid peptides, diprenorphine, another pure opiate antagonist, binds with equally high affinity to both receptor subtypes. Therefore, a second objective was to determine the actions of diprenorphine on drinking in water-deprived rats and squirrel monkeys and to compare the effects of this drug to those of naloxone and naltrexone. All three narcotic antagonists suppressed water consumption of monkeys and rats deprived of water for 18 and 24 hr, respectively. Diprenorphine was the most potent compound tested in both species, producing significant reductions in water consumption of monkeys and rats at systemic doses as low as 0.01 and 0.1 mg/kg respectively. Moreover, diprenorphine was the longest acting of the three drugs in the monkey. These results demonstrate that the narcotic antagonists attenuate drinking in primates as well as in rodents and support the hypothesis that these drugs reduce water intake by interrupting the activity of endogenous opioid pathways mediating drinking behavior.
Bibliographical noteFunding Information:
A prelimlnary report of this study was presented at the 64th annual meeting of the Federatlon of American Societies for Experimental Biology and appears in Fedn. Proc., 39: 995, 1980. This investigatlon was supported in part by USPHS grants TO1 GMO0179, DAO0541 and Research Scientist Development Award KO2 DAO0008 to S.G.H. Present address: Department of Pharmacological and Physiological Sclences, University of Chicago, 947 East 58 Street, Chicago, Illinois 60637. To whom reprint requests should be addressed.