Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse

The vesicular transporter VGAT controls GABA vesicle filling at inhibitory terminals. Here Meye et al. show that cocaine withdrawal reduces VGAT at synapses from pallidum to lateral habenula, thereby decreasing inhibitory transmission. This GABAergic synaptic plasticity is crucial for behaviors modeling cocaine-evoked aversive states and stress-induced relapse.