Impact of gender on corticotropin-releasing factor and noradrenergic sensitivity in cocaine use disorder

Aimee L. McRae-Clark, Angie M. Cason, Amy S. Kohtz, Megan Moran Santa-Maria, Gary Aston-Jones, Kathleen T. Brady

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Responses to stress may be important in understanding gender differences in substance use disorders and may also be a target for development of treatment interventions. A growing body of both preclinical and clinical research supports important underlying gender differences in the corticotropin-releasing factor (CRF) and noradrenergic systems, which may contribute to drug use. Preclinical models have demonstrated increased sensitivity of females to CRF and noradrenergic-induced drug reinstatement compared with males, and, consistent with these findings, human laboratory studies have demonstrated greater sensitivity to corticotropin-releasing hormone (CRH) and noradrenergic stimulation in cocaine-dependent women compared with men. Furthermore, neuroimaging studies have demonstrated increased neural response to stressful stimuli in cocaine-dependent women compared with men as well as showing significant sex differences in the sensitivity of brain regions responsible for regulating the response to CRH. Development of interventions targeting the noradrenergic system and stress response in drug-dependent individuals could have important clinical implications for both women and men.

Original languageEnglish (US)
Pages (from-to)320-327
Number of pages8
JournalJournal of Neuroscience Research
Issue number1-2
StatePublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience


  • corticotropin-releasing hormone
  • guanfacine
  • norepinephrine
  • translational
  • yohimbine


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