Lack of allosteric modulation of striatal GABA A receptor binding and function after cocaine sensitization

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.