Behavioural evidence for a selective GABA-A antagonistic activity of SR 95103 and SR 42641 after intrastriatal injection in mice.

Two pyridazinyl GABA derivatives, SR 95103 and SR 42641 have recently been described as selective GABAA receptor antagonists. We have now investigated the behavioural effects of SR 95103 and SR 42641 after intrastriatal injection in mice. When injected into the right striatum, SR 95103 (0.01-0.5 microgram), SR 42641 (0.0001-0.01 microgram) and bicuculline methiodide (0.005-0.05 microgram) induced contralateral rotations which were antagonized by intraperitoneal injection of muscimol. In contrast, the intrastriatal injection of the GABAA receptor agonist muscimol induced ipsilateral rotations. Muscimol-induced turning was antagonized by SR 95103 (10-30 mg/kg), SR 42641 (1-10 mg/kg) and (+)-bicuculline (0.125-0.5 mg/kg) injected intraperitoneally, but not by strychnine. Intrastriatal glycine also induced ipsilateral rotations which were antagonized by strychnine (0.01-0.3 mg/kg i.p.) but not by (+)-bicuculline, SR 95103 or SR 42641. These results suggest that SR 95103 and SR 42641 induce turning through a selective blockade of GABAA receptors within the striatum.