Opioid antagonists and drinking: evidence of kappa-receptor involvement

Diprenorphine, naloxone, MR-2266-BS and WIN-44,441-3 were compared for their ability to antagonize morphine analgesia and to decrease deprivation-induced drinking in rats. Diprenorphine and naloxone were markedly more potent (32x) than MR-2266-BS and WIN-44,441-3 in antagonizing the analgesic effects of morphine. In contrast, diprenorphine, naloxone and MR-2266-BS decreased deprivation-induced drinking over a similar dose range. The doses required to reduce fluid consumption were higher than those necessary to antagonize morphine. WIN-44,441-3 was ineffective in decreasing drinking. The relatively similar potencies of diprenorphine, naloxone and MR-2266-BS for decreasing deprivation-induced drinking suggest that the effect on drinking involves antagonist activity at a kappa-opioid receptor.