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

The magnitude of behavioral sensitization to cocaine is correlated with dec reased striatal GABA(A) receptor function. We examined whether GABA release from striatal slices is also altered in cocaine-treated rats. Behavioral s ensitization was measured in rats receiving either saline or cocaine (15mg kg(-1)) daily for 14 days. Cocaine-treated rats showed a significant increa se in locomotion and stereotypy over days. Potassium-stimulated endogenous GABA release was measured from superfused striatal slices of these rats. GA BA release was significantly decreased in cocaine-treated rats. However, st riatal slices preloaded with [H-3] GABA exhibited a slight but significant increase in release after cocaine sensitization. Similar treatment with a n onsensitizing dose of cocaine (7.5 mg kg(-1)) did not change endogenous GAB A release. Saline- and cocaine-treated rats showed no differences in striat al glutamic acid decarboxylase activity at either a saturating or K-m conce ntration of glutamate. Therefore, the decrease in endogenous GABA release i s 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 t ransmission, both pre- and postsynaptically, in the striatum of sensitized rats, which could contribute to enhanced striatal output and behavioral sen sitization. (C) 1999 Wiley-Liss, Inc.