Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers

Abstract

Objective: Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.

Method: To test this we compared brain metabolism (using PET and ¹⁸FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video.

Results: Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6%±10) whereas males tended to increase it (+5.5%±18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus).

Conclusions: Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

Figure 1. A. SPM results for the “normalized” metabolic images for Neutral vs Cocaine-cues video conditions in the Females.

Comparison correspond to Neutral > Cocaine-cues for uncorrected threshold p_u<0.001 cluster >200 voxels. There were no regions where metabolism was higher during the Cocaine-cues than the Neutral conditions. B. SPM results for the “normalized” metabolic images for Neutral vs Cocaine-cues video conditions in the Males. Comparison correspond to Neutral > Cocaine-cues for uncorrected threshold p_u<0.005 cluster >200 voxels; we used this lower threshold since there were no significant differences for p_u<0.001. There were no regions where metabolism was higher during the Cocaine-cues than the Neutral conditions.

Figure 2. SPM results for the gender by cues (Neutral > Cocaine-cues) interaction on the “normalized” metabolic images.

Comparison correspond to Females > Males for uncorrected threshold p_u<0.001 cluster >200 voxels. There were no regions where males had larger changes than females.