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.