Cocaine sensitization and accumbens shell plasticity depend on biological sex and gonadal hormones in C57BL/6J mice.

ABSTRACT: Biological sex as a defining variable in drug sensitivity remains poorly understood. Here, we combine behavioral and electrophysiological analyses to examine the influence of sex and gonadal hormones on cocaine-induced psychomotor sensitization and nucleus accumbens shell (NAcSh) plasticity in the prominent C57BL/6J mouse strain. Males exhibited greater cocaine-evoked locomotor activity than females; castration attenuated responses, whereas ovariectomy enhanced them. This behavioral phenotype is opposite to what occurs in rats. A 10-14 day abstinence period abolished the sex difference in intact animals, and gonadectomy reduced cocaine-induced behavioral plasticity. Recordings from 309 medium spiny neurons revealed sex-dependent NAcSh plasticity. In males, cocaine decreased neuronal excita

SUBMITTER: Chapp AD 

PROVIDER: S-EPMC12724412 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature