GABA(A) receptor α subunits differentially contribute to diazepam tolerance after chronic treatment.

ABSTRACT:

Background

Within the GABA(A)-receptor field, two important questions are what molecular mechanisms underlie benzodiazepine tolerance, and whether tolerance can be ascribed to certain GABA(A)-receptor subtypes.

Methods

We investigated tolerance to acute anxiolytic, hypothermic and sedative effects of diazepam in mice exposed for 28-days to non-selective/selective GABA(A)-receptor positive allosteric modulators: diazepam (non-selective), bretazenil (partial non-selective), zolpidem (α(1) selective) and TPA023 (α(2/3) selective). In-vivo binding studies with [(3)H]flumazenil confirmed compounds occupied CNS GABA(A) receptors.

Results

Chronic diazepam treatment resulted in tolerance to diazepam's acute anxiolytic, hypothermic and sedative effects. In mice treated chronic

SUBMITTER: Vinkers CH 

PROVIDER: S-EPMC3418228 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature