Early-life stress and ovarian hormones alter transcriptional regulation in the nucleus accumbens resulting in sex-specific responses to cocaine [RNA-Seq]. Early-life stress and ovarian hormones alter transcriptional regulation in the nucleus accumbens resulting in sex-specific responses to cocaine [RNA-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: RNA-seq experiments were designed to determine differential RNA expression in the nucleus accumbens of male and female mice, among both controls and animals subjected to early life stress in the form of 2 weeks maternal separation for 2 hours per day from postnatal day 1-14. Six biological replicates (each composed of bilateral nucleus accumbens) were tested per group. Female groups were balanced by the estrous cycle containing and equal number for proestrus/estrus animals and metestrus/diestrus animals.