Sex differences in brain activation during stress imagery in abstinent cocaine users: A functional magnetic resonance imaging study

Background Because stress mediates drug seeking and relapse, and sex differences have been observed in stress and in the development of cocaine addiction, in this study we used functional neuroimaging to examine the effect of sex on stress responses in abstinent cocaine users. Methods In a functional magnetic resonance imaging session, 17 male and 10 female cocaine-dependent subjects participated in script-guided imagery of neutral or stress situations. Subjects rated imagery vividness, anxiety, and cocaine craving for each trial. Brain activation during the stress and neutral imagery periods relative to their own baseline was examined in individual subjects. Sex contrast was obtained in second-level group analysis. Results Female subjects demonstrated more activation, compared with male subjects, in left middle frontal, anterior cingulate, and inferior frontal cortices and insula, and right cingulate cortex during stress imagery. Region of interest analysis showed that the change of activity in left anterior cingulate and right posterior cingulate cortices both correlated inversely with the change of craving rating during stress imagery. Conclusions The greater left frontolimbic activity in women suggests that women might use more verbal coping strategies than do men while experiencing stress. The results also suggest a distinct role of the cingulate cortices in modulating stress-induced cocaine craving.