Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence.

Abstract

Methamphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. The authors recently reported that decreases in dopamine transporters (used as markers of dopamine terminals) in the striatum of methamphetamine abusers recover with protracted abstinence and that relative to comparison subjects, recently detoxified methamphetamine abusers have lower metabolism in the striatum and thalamus. In this study, the authors assessed whether metabolism recovers with protracted abstinence. Brain glucose metabolism was measured with positron emission tomography and [18F]fluorodeoxyglucose in five methamphetamine abusers who were evaluated after both a short (<6 months) and protracted (12-17 months) abstinence interval, eight methamphetamine abusers tested only after protracted abstinence, and 11 comparison subjects who were not drug users. Significantly greater thalamic, but not striatal, metabolism was seen following protracted abstinence relative to metabolism assessed after a short abstinence interval, and this increase was associated with improved performance in motor and verbal memory tests. Relative to the comparison subjects, the methamphetamine abusers tested after protracted abstinence had lower metabolism in the striatum (most accentuated in the caudate and nucleus accumbens) but not in the thalamus. The persistent decreases in striatal metabolism in methamphetamine abusers could reflect long-lasting changes in dopamine cell activity, and decreases in the nucleus accumbens could account for the persistence of amotivation and anhedonia in detoxified methamphetamine abusers. The recovery of thalamic metabolism could reflect adaptation responses to compensate for the dopamine deficits, and the associated improvement in neuropsychological performance further indicates its functional significance. These results suggest that while protracted abstinence may reverse some of the methamphetamine-induced alterations in brain function, other deficits persist.