Opposite effects of midazolam and β-carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo mudialysis

Abstract This report describes the effects of midazolam and β-carboline-3-carboxylate ethyl ester (β-CCE) on extracellular concentrations of dopamine in the nucleus accumbens of freely moving rats measured by in vivo mudialysis. The two compounds had opposite effects, midazolam (0.075 and 0.15 mg/kg i.v.) dose dependently decreasing, and β-CCE (3 and 10 mg/kg i.p.) dose dependently increasing, dialysate concentrations of dopamine. Flumazenil (6 μg/kg i.v.) did not affect the efflux of dopamine but it prevented the effects of both midazolam and β-CCE on dopamine efflux. N 6 -Cyclohexyladenosine (0.1, and 1 mg/kg i.p.), a seletive adenosine A 1 agonist, dose dependently increased the efflux of dopamine. This effect was blocked by 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg i.p.), a selective adenosine A 1 receptor antagonist, a dose which given alone did not affect dopamine efflux; responses to midazolam were not affected. 3,7-Dimethyl-1-propargylxanthine (1 and 3 mg/kg i.p.), a selective adenosine A 2 receptor antagonist, did not mimic the effects of β-CCE. The results suggest that midazolam and β-CCE modulate dopamine release in the nucleus accumbens by an action at the benzodiazepine binding site associated with the GABA A receptor complex.