Repeated cocaine injections decrease the function of striatal gamma-aminobutyric acid(A) receptors.

Although behavioral sensitization to cocaine is commonly thought to involve increased dopamine (DA) neurotransmission in nigrostriatal and mesolimbic pathways, it is possible that alterations in the characteristics of other neurotransmitters, such as gamma-aminobutyric acid (GABA), contribute to cocaine-induced behavioral changes. The function of GABA(A) receptors to transport chloride was assessed in striatum and other brain regions of male rats that had received daily injections of cocaine (15 mg/kg i.p.) or saline for 5 to 14 days. GABA-stimulated 36Cl uptake in striatal microsacs was decreased significantly in animals receiving cocaine treatments sufficient to cause behavioral sensitization, and the magnitude of this decrease paralleled the magnitude of cocaine sensitization. There was no effect of cocaine treatment on GABA-stimulated uptake in cortex or substantia nigra nor was basal uptake affected by cocaine exposure in any of three regions. Muscimol-stimulated uptake was similarly decreased in striatal microsacs from female rats exposed to daily cocaine (10 mg/kg i.p.) injections for 14 days. This decrease in receptor function was not due to a direct effect of cocaine on GABA(A) receptors because neither in vitro nor in vivo acute cocaine exposure affected uptake in any way. Thus, GABA(A) receptor function in striatum may be selectively decreased by cocaine treatment which may contribute to changes in behavioral sensitization caused by cocaine.