Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users

Objective: Previous studies found functional changes in the frontal brain r egion and regions with projections to the frontal lobe in cocaine users. Th e aim of this study was to investigate persistent neurochemical changes in the frontal lobes of subjects with a history of crack cocaine dependence an d to determine whether these changes are different in male and female users . Method: The frontal gray and white matter of 64 young asymptomatic and ab stinent (>5 months) cocaine users (34 male and 30 female) and 58 healthy co mparison subjects without a history of drug abuse was evaluated with locali zed proton magnetic resonance spectroscopy (H-1-MRS). Results: Two-way anal ysis of variance showed significant cocaine effects on the concentration of frontal gray matter N-acetyl compounds, on the ratio of frontal white matt er N-acetyl compounds to creatine levels, on frontal gray and white matter myoinositol levels, and on the ratio of myoinositol to creatine. Significan t gender effects were observed for frontal gray matter choline-containing c ompounds, the ratio of choline-containing compounds to creatine, and the pe rcentage of CSF in both gray and white matter. Interaction effects of cocai ne and gender were observed for creatine, N-acetyl/creatine ratio, and myoi nositol/creatine ratio in frontal white matter. Conclusions: Cocaine use is associated with neuronal injury (with decreased N-acetyl compounds) in the frontal cortex and glial activation (with increased myoinositol) in both f rontal gray and white matter. In the frontal lobe, cocaine affects male use rs differently than female users. Future studies on the effects of cocaine abuse should control for the effects of gender-specific neurotoxicity.