The whole-cell patch-clamp technique was used to compare the properties of native GABAA receptors in Purkinje and striatal neurons acutely dissociated from neonatal rat brains (7-11 days old). In symmetrical chloride concentrations and at a negative holding voltage, GABA induced inward currents in a concentration-dependent manner with EC50 values of 4 and 8 uM in Purkinje and striatal neurons, respectively. Diazepam potentiated the current induced by 1 uM GABA in Purkinje and striatal neurons with EC50 values of 28 and 42 nM and maximal potentiations of 128 and 182%, respectively. Zolpidem potentiated this GABA-induced current in Purkinje and striatal neurons with EC50 values of 33 and 195 nM and maximal potentiations of 189 and 236%, respectively. These results show that zolpidem, in contrast to diazepam, functionally discriminates subtypes of native GABAA receptors. Zolpidem has greater affinity for GABAA receptors containing omega 1 (Purkinje cells) than for those with omega 2 (striatum) sites and has higher intrinsic activity at these receptors than diazepam. These properties of zolpidem may contribute to its hypnoselective profile.