Kappa Opioid Receptors Control a Stress-Sensitive Brain Circuit and Drive Cocaine Seeking.

ABSTRACT: Stress is a potent trigger for drug-seeking behaviors in both rodents and humans with a history of substance use. Kappa opioid receptors (kORs) play a critical role in mediating stress responses. Our previous studies in the ventral tegmental area (VTA) demonstrated that acute stress activates kORs to block long-term potentiation at GABA_A synapses on dopamine neurons (LTP_GABA) and triggers stress-induced reinstatement of cocaine seeking. Here we identify the specific GABAergic afferents affected by stress, the precise localization of kORs within the VTA, and show that VTA kOR activation is sufficient to drive reinstatement. In male and female mice, we optogenetically activated specific GABAergic afferents and found that nucleus accumbens (NAc)-to-VTA, but not lateral h

SUBMITTER: Martinez Damonte V 

PROVIDER: S-EPMC12548717 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature