Differential effects on GABAA receptor gamma 2-subunit messenger RNA by tolerance to and withdrawal from pentobarbital--an in situ hybridization study.
The heterogeneity of the GABAA receptors has been confirmed structurally and functionally. The present study demonstrates the pharmacological heterogeneity of the GABAA receptors. Rats were rendered tolerant to pentobarbital by continuous intracerebroventricular infusion via osmotic minipumps and abruptly withdrawn from pentobarbital. In situ hybridization of mRNA coding for the GABAA receptor gamma 2-subunit showed decreases of mRNA levels in superior and inferior colliculus in pentobarbital tolerant rats compared to rats in withdrawal. In rats 24-hr after withdrawal from pentobarbital, increases of mRNA levels in neocortex, piriform cortex and in granular and Purkinje cell layers of the cerebellum were observed. These results indicate the fast adaptation of GABA synapses in response to abrupt withdrawal from chronic pentobarbital treatment. The differential responsiveness seen in different areas further confirms the pharmacological heterogeneity of the GABAA receptors. The observed increases and decreases of mRNA may underlie, at least in part, the previously reported changes in Bmax of GABAA receptor ligand binding sites.
Tseng
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Wellman
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D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D004361:Drug Tolerance; D017403:In Situ Hybridization; D010424:Pentobarbital / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000235:genetics*; D013462:Sulfur Radioisotopes
D012333:RNA, Messenger; D018079:Receptors, GABA; D013462:Sulfur Radioisotopes; D010424:Pentobarbital