Elsevier

Neuropharmacology

Volume 35, Issue 2, February 1996, Pages 137-145
Neuropharmacology

Zolpidem functionally discriminates subtypes of native GABAA receptors in acutely dissociated rat striatal and cerebellar neurons

https://doi.org/10.1016/0028-3908(95)00158-1Get rights and content

Abstract

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 μM in Purkinje and striatal neurons, respectively. Diazepam potentiated the current induced by 1 μM 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 ω1 (Purkinje cells) than for those with ω2 (striatum) sites and has higher intrinsic activity at these receptors than diazepam. These properties of zolpidem may contribute to its hypnoselective profile.

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