Sex differences have been reported in various phases of substance abuse, including relapse. In general, women show greater propensity to drug relapse than men, owing perhaps to divergent withdrawal experiences and increased reactivity to internal (emotional) and external (drug-associated) cues. Animal research tends to parallel human findings, revealing enhanced reinstatement of drug administration in females than males. Moreover, differences in vulnerability to relapse/reinstatement have been documented in women and female rodents across the ovarian cycles. Thus ovarian hormones seem to play an important role in determining susceptibility to relapse. Indeed, ovarian hormones interact with many of the neural circuits implicated in drug-primed, cue-instigated, and stress-induced relapse. By understanding the effects of ovarian hormones on the neural and behavioral mechanisms of drug relapse, sex differences and cyclical variations in relapse susceptibility can be elucidated and more effective treatment strategies can be explored.
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