Neurochemical adaptation to cocaine abuse: reduction of N-acetyl aspartate in thalamus of human cocaine abusers

Background: The aim of this study was to determine the existence of, and possible mechanisms for, chronic cocaine use-induced neurotoxicity in the human brain. Because in vivo magnetic resonance spectroscopy (MRS) provides a noninvasive way to detect biochemical and physiological changes in the brain, we sought to specifically determine the neurochemical adaptations in chronic cocaine-dependent subjects. Methods: Twenty-one cocaine users and 13 non–drug-using, age-matched normal volunteers were recruited for an in vivo proton MRS study. Following screening that included physical examination, histories, and blood testing, cocaine group subjects received a spectral scan on a 1.5-T GE Signa scanner. Spectra were obtained from the left basal ganglia and/or the left thalamus from subjects in both groups using an rf bird-cage type head coil with single-voxel localization. Results: The level of N-acetyl aspartate in the region of left thalamus was lower (17%) in the chronic cocaine user group but not in the region of left basal ganglia, compared with the control group. Conclusions: These results suggest that chronic cocaine use may induce abnormal neurochemical activity and a state of neuronal dysregulation and/or neurotoxicity. It will now be important to determine if these alterations are reversible during withdrawal and what the functional implications of this observation are with respect to cognitive function and drug relapse.