Zolpidem functionally discriminates subtypes of native GABA(A) receptors in acutely dissociated rat striatal and cerebellar neurons

The whole-cell patch-clamp technique was used to compare the properties of native GABA(A) 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 EC(50) values of 4 and 8 mu M in Purkinje and striatal neurons, respectively. Diazepam potentiated the current induced by 1 mu M GABA in Purkinje and striatal neurons with EC(50) 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 EC(50) 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 GABA(A) receptors. Zolpidem has greater affinity for GABA(A) 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.