Ventral tegmental area astrocytes modulate cocaine reward by tonically releasing GABA.

ABSTRACT: Addictive drugs increase ventral tegmental area (VTA) dopamine (DA) neuron activity through distinct cellular mechanisms, one of which involves disinhibition of DA neurons by inhibiting local GABA neurons. How drugs regulate VTA GABA neuron activity and drive addictive behaviors remains poorly understood. Here, we show that astrocytes control VTA GABA neuron activity in cocaine reward via tonic inhibition in mice. Repeated cocaine exposure potentiates astrocytic tonic GABA release through volume-regulated anion channels (VRACs) and augments tonic inhibition of VTA GABA neurons, thus downregulating their activities and disinhibiting nucleus accumbens (NAc) projecting DA neurons. Attenuation of tonic inhibition by either deleting Swell1 (Lrrc8a), the obligatory subunit of VRACs, in VTA astro

SUBMITTER: Yang J 

PROVIDER: S-EPMC10079641 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature