Brain choline acetyltransferase activity in chronic, human users of cocaine, methamphetamine, and heroin

Cognitive impairment has been reported in some chronic users of psychostimu lants, raising the possibility that long-term drug exposure might damage br ain neuronal systems, including the cholinergic system, which are responsib le for normal cognition. We measured the activity of choline acetyltransfer ase (ChAT), the marker enzyme for cholinergic neurones, in autopsied brain of chronic users of cocaine, methamphetamine, and, for comparison, heroin. As compared with the controls, mean ChAT levels were normal in all cortical and subcortical brain areas examined. However, the two of 12 methamphetami ne users, who had the highest brain/blood drug levels at autopsy, had a sev ere (up to 94%) depletion of ChAT activity in cerebral cortex, striatum, an d thalamus. Based on the subjects examined in the present study, our neuroc hemical data suggest that brain cholinergic neurone damage is unlikely to b e a typical feature of chronic use of cocaine, methamphetamine, or heroin, but that exposure to very high doses of methamphetamine could impair, at le ast acutely, cognitive function requiring a normal nucleus basalis choliner gic neuronal system. Reduced brain ChAT might be explained in part by a hyp erthermia-related mechanism as low ChAT levels have also been observed in b rain of some patients with neuroleptic drug-associated hyperthermia. Studie s of cognitive and brain cholinergic status in high dose users of MA are wa rranted.