Early-life stress and ovarian hormones alter transcriptional regulation in the nucleus accumbens resulting in sex-specific responses to cocaine [ATAC-Seq]. Early-life stress and ovarian hormones alter transcriptional regulation in the nucleus accumbens resulting in sex-specific responses to cocaine [ATAC-Seq]

Cocaine use disorder affects people across genders, although women are reported to be more sensitive than men to cocaine’s addictive properties. Our study highlights that cocaine use in women and other menstruating individuals may involve complex effects of ovarian hormones that interact with internal factors (such as negative affective state) and external risk factors such as stress and, for the first time, we reveal the molecular substrates through which female-specific factors can induce stronger and longer-lasting, sex-specific responses to cocaine. Overall design: ATAC-seq experiments were designed to determine chromatin accessibility profiles of nucleus accumbens neurons in young adult females in two different stages of the estrous cycle (proestrus and diestrus) and in age-matched males between controls and animals that received 10mg/kg of cocaine (i.p.) and were sacrificed 1 hour after injection. 2-3 biological replicates (each pooled from three animals) were tested per group.