| First Author | Rocks D | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 10 | Pages | 113187 |
| PubMed ID | 37777968 | Mgi Jnum | J:347554 |
| Mgi Id | MGI:7550285 | Doi | 10.1016/j.celrep.2023.113187 |
| Citation | Rocks D, et al. (2023) Early-life stress and ovarian hormones alter transcriptional regulation in the nucleus accumbens resulting in sex-specific responses to cocaine. Cell Rep 42(10):113187 |
| abstractText | Early-life stress and ovarian hormones contribute to increased female vulnerability to cocaine addiction. Here, we reveal molecular substrates in the reward area, the nucleus accumbens, through which these female-specific factors affect immediate and conditioning responses to cocaine. We find shared involvement of X chromosome inactivation-related and estrogen signaling-related gene regulation in enhanced conditioning responses following early-life stress and during the low-estrogenic state in females. Low-estrogenic females respond to acute cocaine by opening neuronal chromatin enriched for the sites of DeltaFosB, a transcription factor implicated in chronic cocaine response and addiction. Conversely, high-estrogenic females respond to cocaine by preferential chromatin closing, providing a mechanism for limiting cocaine-driven chromatin and synaptic plasticity. We find that physiological estrogen withdrawal, early-life stress, and absence of one X chromosome all nullify the protective effect of a high-estrogenic state on cocaine conditioning in females. Our findings offer a molecular framework to enable understanding of sex-specific neuronal mechanisms underlying cocaine use disorder. |
