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

The magnitude of behavioral sensitization to cocaine is correlated with decreased striatal GABAA 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 [3H]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 Km 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. Synapse 34:103–110, 1999. © 1999 Wiley‐Liss, Inc.