Increased response of cerebellar cGMP to kainate but not NMDA or quisqualate following barbital withdrawal from dependent rats.
Female Sprague-Dawley rats were maintained on a diet of powdered food containing barbital for 8 weeks before the drug was abruptly withdrawn. Twenty-four hours later both barbital-dependent and control rats were injected intracerebroventricular (i.c.v.) with saline or one of four doses of kainic acid (KA) or in a separate experiment with saline or one of three doses of N-methyl-D-aspartic acid (NMDA) or of quisqualic acid (QA). After 4.5 min, the animals were killed by focused microwave irradiation, and the cerebella were collected. The levels of cyclic guanosine 3',5' monophosphate (cGMP) were markedly elevated in the cerebella of barbital-withdrawn rats when compared to controls. When compared to saline treatment, KA, at all dosages, resulted in a significantly greater elevation of cerebellar cGMP in the barbital-withdrawn rats than was induced by drug withdrawal alone. Only the two higher dosages of KA produced a significant elevation of this parameter in the control rats. Unlike KA, neither QA or NMDA produced any greater elevations of cGMP in barbital withdrawn rats than were induced by drug withdrawal alone. These collective results suggest that there is an increase in the response to KA but not QA or NMDA following the withdrawal of barbital from dependent rats.
McCaslin
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PP
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Morgan
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WW
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001462:Barbital / Q000009:adverse effects*; D001463:Barbiturates / Q000009:adverse effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology*; D016202:N-Methylaspartate; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*
D001463:Barbiturates; D009467:Neuromuscular Depolarizing Agents; D010069:Oxadiazoles; D001224:Aspartic Acid; D001462:Barbital; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D006152:Cyclic GMP; D007608:Kainic Acid