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 micrograms (per mouse), suppressed drinking only in the polydipsic mice, while the higher dose (5.0 micrograms) 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 micrograms), 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.
Katafuchi
T
T
Department of Physiology, State University of New York, Brooklyn 11203.
Hattori
Y
Y
Nagatomo
I
I
Koizumi
K
K
D000818:Animals; D004327:Drinking Behavior / Q000187:drug effects* / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005824:Genetics, Behavioral; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D051379:Mice; D008817:Mice, Mutant Strains; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa
D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone