KAPPA-OPIOID ANTAGONIST STRONGLY ATTENUATES DRINKING OF GENETICALLY POLYDIPSIC MICE

Effects of opioid antagonists on the genetic polydipsia of the STR/N strain of mice were investigated. Naltrexone (0.5-5.0 mg/kg) injected subcutaneously before dark period attenuated spontaneous drinking for the first 3 h after injection only in the inbred polydipsic mice (STR/N), whose water intake was 5 times that of controls (non-polydipsic mutant, STR/1N, and Swiss/Webster mice). The highest dose (5 mg/kg) of naltrexone administration reduced drinking also during the next 3-6 h period and overnight feeding. Cerebroventricular (i.c.v.) injection of naltrexone, 1.0 and 2.5-mu-g (per mouse), suppressed drinking only in the polydipsic mice, while the higher dose (5.0-mu-g) attenuated drinking and feeding of both the polydipsic mice and their controls. However, i.c.v. injection of specific kappa-receptor antagonist, nor-binaltorphimine (nor-BNI, 0.5-2.5-mu-g), suppressed drinking only in the polydipsic strain of mice at one-half dose of that needed for naltrexone. Furthermore, even a higher dose of nor-BNI administration was without effect on food intake in all strains. These findings suggest that the central opioid system plays an important role in causing the polydipsia in the STR/N mice, probably through the kappa-opioid receptor.