Endogenous GABA release is reduced in the striatum of cocaine-sensitized rats

The magnitude of behavioral sensitization to cocaine is correlated with decreased striatal GABA(A) receptor function. We examined whether GABA release from striatal slices is also altered in cocaine-treated rats. Behavioral sensitization was measured in rats receiving either saline or cocaine (15 mg kg(-1)) daily for 14 days. Cocaine-treated rats showed a significant increase in locomotion and stereotypy over days. Potassium-stimulated endogenous GABA release was measured from superfused striatal slices of these rats. GABA release was significantly decreased in cocaine-treated rats. However, striatal slices preloaded with [(3)H]GABA exhibited a slight but significant increase in release after cocaine sensitization. Similar treatment with a nonsensitizing dose of cocaine (7.5 mg kg(-1)) did not change endogenous GABA release. Saline- and cocaine-treated rats showed no differences in striatal glutamic acid decarboxylase activity at either a saturating or K(m) concentration of glutamate. Therefore, the decrease in endogenous GABA release is not due to a decrease in GABA synthesis, but may reflect changes in GABA storage pools. These data are consistent with an overall decrease in GABA transmission, both pre- and postsynaptically, in the striatum of sensitized rats, which could contribute to enhanced striatal output and behavioral sensitization.