Autoradiographic study of [3H]flunitrazepam binding sites in the subnuclei of the thalamus of rats rendered tolerant to and dependent on pentobarbital.
We examined changes in benzodiazepine binding sites labeled by [3H]flunitrazepam in five nuclei of the thalamus, the central medial, central lateral, intermediodorsal, ventroposterior, and laterodorsal nuclei, in rats made tolerant to and dependent on pentobarbital. Animals were made tolerant by intracerebroventricular infusion with pentobarbital (300 microg (10 microl)(-1) h(-1) for six days) through pre-implanted cannulae. Pentobarbital dependence was assessed 24 h after abrupt withdrawal from pentobarbital. Pentobarbital-tolerant rats showed no significant change in [3H]flunitrazepam binding sites (Bmax and Kd) in any nucleus examined in the thalamus. In the rats made dependent on pentobarbital, significant increases in the Bmax of [3H]flunitrazepam binding without changes in Kd were noted in central medial and central lateral nuclei. GABAergic (gamma-aminobutyric acid) neurons in the ventrobasal nucleus and in nuclei in the midline group are important in seizure regulation and arousal. These findings suggest that alterations of benzodiazepine receptors in certain nuclei of thalami are involved in the physiological changes induced by pentobarbital dependence. There were no changes in the binding parameters for [3H]flunitrazepam in pentobarbital-tolerant rats.
Suzuki
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, USA.
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Wellman
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D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D004361:Drug Tolerance; D005445:Flunitrazepam / Q000493:pharmacokinetics*; D018757:GABA Modulators / Q000493:pharmacokinetics*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism; D013787:Thalamic Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D014316:Tritium; D005445:Flunitrazepam; D010424:Pentobarbital