Inhibitory and excitatory synaptic neuroadaptations in the diazepam tolerant brain.

ABSTRACT: Benzodiazepine (BZ) drugs treat seizures, anxiety, insomnia, and alcohol withdrawal by potentiating γ2 subunit containing GABA type A receptors (GABA_ARs). BZ clinical use is hampered by tolerance and withdrawal symptoms including heightened seizure susceptibility, panic, and sleep disturbances. Here, we investigated inhibitory GABAergic and excitatory glutamatergic plasticity in mice tolerant to benzodiazepine sedation. Repeated diazepam (DZP) treatment diminished sedative effects and decreased DZP potentiation of GABA_AR synaptic currents without impacting overall synaptic inhibition. While DZP did not alter γ2-GABA_AR subunit composition, there was a redistribution of extrasynaptic GABA_ARs to synapses, resulting in higher levels of synaptic BZ-in

SUBMITTER: Lorenz-Guertin JM 

PROVIDER: S-EPMC10578451 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature