Binding characteristics of t-[35S]butylbicyclophosphorothionate in discrete brain regions of rats made tolerant to and dependent on pentobarbital.
The effects of acute and continuous pentobarbital administration by pellet implantation on binding characteristics of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) in discrete regions of rat brains were examined. Acute administration of pentobarbital (60 mg/kg, s.c.) affected neither the KD nor the Bmax values of [35S]TBPS binding in any of the regions studied. The cerebella of pentobarbital-tolerant rats had an increased density of [35S]TBPS binding sites with no change in their apparent affinity. There were no significant changes in the binding characteristics in the frontal cortex (FC), the striatum (ST), and the substantia nigra (SN) of these animals. Twenty-four hours after removal of the pentobarbital pellets, a significant decrease in the latency of onset of first twitch response induced by pentylenetetrazol (PTZ) (50 mg/kg, i.p.) was observed. In addition, the density of [35S]TBPS binding sites was significantly increased in the FC, the SN, and the cerebellum but not in the ST. In all brain regions studied, placebo pellet implantation and pentobarbital tolerance and dependence caused no changes in the apparent affinity of [35S]TBPS binding or the IC50 of pentobarbital for the inhibition of [35S]TBPS binding. These results suggest that [35S]TBPS binding was significantly increased following the withdrawal of the pentobarbital pellets without altering intrinsic coupling activity of barbiturate recognition sites and convulsant binding sites and that these increases in [35S]TBPS binding are related to the increased susceptibility to seizures induced by PTZ in rats made dependent on pentobarbital.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Saunders
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Lim
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005625:Frontal Lobe / Q000378:metabolism; D008297:Male; D010424:Pentobarbital; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019966:Substance-Related Disorders / Q000378:metabolism*; D014018:Tissue Distribution
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; C037476:tert-butylbicyclophosphorothionate; D010424:Pentobarbital; D010433:Pentylenetetrazole