title: Lack of allosteric modulation of striatal GABA(A) receptor binding and function after cocaine sensitization.
abstract: GABA(A) receptor binding after repeated cocaine has been shown to be either increased as indicated by benzodiazepine binding or decreased as indicated by convulsant-site binding. We measured the GABA binding site with [3H]-muscimol binding to GABA(A) receptors and found no differences between saline- and cocaine-sensitized rats. Allosteric modulation of [3H]-muscimol binding with flunitrazepam was also unchanged after cocaine sensitization. In addition, [3H]-flunitrazepam binding and allosteric modulation of [3H]-flunitrazepam binding with GABA was unchanged after 1 day withdrawal from repeated cocaine. GABA(A) receptor function and allosteric modulation of GABA(A) receptor function measured by GABA-stimulated Cl(-) uptake was also unchanged after withdrawal from repeated cocaine. Finally, in vitro cocaine reduced GABA(A) receptor function in striatal microsacs of saline- and cocaine-treated rats. In conclusion, repeated cocaine did not change the coupling of the GABA(A) receptor between the GABA and benzodiazepine (BZD) binding site after 1 day withdrawal.
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida, 1600 Southwest Archer Road, P.O. Box 100487, Gainesville, FL 32610-0487, USA. jungb@musc.edu
authors.forename: B J
authors.initials: BJ
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Peris
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000502:physiology
chemical_list: D018765:Dopamine Uptake Inhibitors; D011963:Receptors, GABA-A; D003042:Cocaine