Cannabinoid receptor agonist WIN 55,212-2 inhibits rat cortical dialysate gamma-aminobutyric acid levels

The effects of the cannabinoid receptor agonist WIN 55,212-2 (0.1-5 mg/kg i .p.) on endogenous extracellular gamma -aminobutyric acid (GABA) levels in the cerebral cortex of the awake rat was investigated by using microdialysi s. WIN 55,212-2 (1 and 5 mg/kg i.p.) was associated with a concentration-de pendent decrease in dialysate GABA levels (-16% +/- 4% and -26% +/- 4% of b asal values, respectively). The WIN 55,212-2 (5 mg/kg i.p.) induced-inhibit ion was counteracted by a dose (0.1 mg/kg i.p.) of the CB, receptor antagon ist SR141716A, which by itself was without effect on cortical GABA levels. These findings suggest that cannabinoids decrease cortical GABA levels in v ivo, an action that might underlie some of the cognitive and behavioral eff ects of acute exposure to marijuana. (C) 2001 Wiley-Liss, Inc.