Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens.

ABSTRACT: Drug-induced enhanced dopamine (DA) signaling in the brain is a canonical mechanism that initiates addiction processes. However, indirect evidence suggests that cocaine also triggers non-canonical, DA-independent, mechanisms that contribute to behavioral responses to cocaine, including psychomotor sensitization and cocaine self-administration. Identifying these mechanisms and determining how they are initiated is fundamental to further our understanding of addiction processes. Using physiologically relevant in vitro tractable models, we found that cocaine-induced hypoactivity of nucleus accumbens shell (NAcSh) medium spiny neurons (MSNs), one hallmark of cocaine addiction, is independent of DA signaling. Combining brain slice studies and site-directed mutagenesis in HEK293T cells, we found

SUBMITTER: Delint-Ramirez I 

PROVIDER: S-EPMC7042730 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature