Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence - PubMed (original) (raw)

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Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence

N D Volkow et al. J Neurosci. 2001.

Abstract

Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

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Figures

Fig. 1.

Fig. 1.

Brain images of the distribution volume of [11C]_d-threo_-methylphenidate in a control and a METH abuser. Images shown were obtained at the level of the striatum (images to the left) and the cerebellum (images to the right), and they are from a normal control and a METH abuser evaluated twice, during short and protracted abstinence. Notice the significant increases in binding in striatum in the METH abuser with protracted abstinence.

Fig. 2.

Fig. 2.

Individual measures for DAT availability in the five METH abusers tested twice during short and protracted abstinence. Measures of DAT availability (_B_max/_K_d) were significantly increased with protracted abstinence in caudate (p < 0.003) and putamen (p < 0.05). Repeated-measures ANOVA.

Fig. 3.

Fig. 3.

A, Correlation between changes in DAT in putamen between the first and second evaluations and the reported doses (r = 0.88; df = 4;p < 0.05) and years of METH used (r = 0.83; df = 4; p < 0.08). B, Correlation between changes in DAT in striatum between the first and second evaluations and the days elapsed between evaluations (r = 0.92; df = 4;p < 0.05).

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