Effects of the opiates on the paraventricular nucleus in genetically polydipsic mice.
The inbred mice, STR/N, are known to possess extreme polydipsia with no known abnormality in vasopressin system and the kidney function. Our previous studies indicate that the opiate antagonists given intracerebroventricularly strongly attenuated spontaneous drinking. To determine the site(s) of action, the present study was undertaken. Microinjections of naltrexone methobromide and a selective kappa-receptor antagonist, nor-binaltorphimine (nor-BNI), into the paraventricular nucleus of the hypothalamus (PVN) greatly attenuated drinking of the STR/N for 0.5 to 16 h after injections, while in the two control groups, non-polydipsic STR/1N and Swiss/Webster strains, drinking was not affected by the injections. Food intake was not much altered in all groups. Studies of PVN neurons in vitro (n = > 160 for each group) showed that basal firing rates and patterns were similar in the STR/N and the control groups. Morphine added to the medium inhibited some but excited none in all strains tested. The threshold for the inhibitory action was higher in the polydipsic STR/N mice (10(-8) M), compared to that in the control, S/W mice (10(-9) M). Further, a proportion of neurons inhibited by morphine in the PVN was significantly smaller (P < 0.01) in the STR/N (41.7%), compared to that in the control (64.9%). Dynorphin had very similar effect to that of morphine, but the proportion of cells inhibited was 25.4% in the STR/N, and 70.4% in the S/W. Prior applications of naloxone to the medium prevented the action of both morphine and dynorphin. Under the synaptic blockade (in a low Ca2+ and high Mg2+ medium) the inhibitory effect of the opiates persisted. We concluded that the PVN is at least one of the possible sites where the opiates are acting to cause the polydipsia in the STR/N mice.
Nagatomo
I
I
Department of Physiology, State University of New York, Health Science Center, Brooklyn 11203.
Katafuchi
T
T
Koizumi
K
K
D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds; D013569:Synapses / Q000187:drug effects; D013894:Thirst / Q000502:physiology*
D009292:Narcotic Antagonists; D009294:Narcotics; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; D009020:Morphine