Abuse-related effects of subtype-selective GABA_A receptor positive allosteric modulators in an assay of intracranial self-stimulation in rats.

ABSTRACT:

Rationale

GABA_A positive allosteric modulators (GABA_A PAMs), such as diazepam and zolpidem, are used clinically for anxiety and insomnia, but abuse liability is a concern. Novel GABA_A PAMS may have lower abuse liability while retaining clinical utility.

Objective

The present study compared abuse-related effects of the non-selective GABA_A PAM diazepam, the α1-selective GABA_A PAM zolpidem, and three novel GABA_A PAMs (JY-XHe-053, XHe-II-053, and HZ-166) using intracranial self-stimulation (ICSS) in rats. These novel compounds have relatively low efficacy at α1-, α2-, and α3-containing GABA_A receptors, putative in vivo selectivity at α2/α3-containing GABA_A receptors, and produce anxiolytic-li

SUBMITTER: Schwienteck KL 

PROVIDER: S-EPMC5875719 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature