Do Preclinical Findings of Methamphetamine-Induced Motor Abnormalities Translate to an Observable Clinical Phenotype?

Abstract

This review summarizes the preclinical literature of the effects of methamphetamine (MA) on subcortical dopaminergic and GABAergic mechanisms underlying motor behavior with the goal of elucidating the clinical presentation of human MA-induced movement disorders. Acute and chronic MA exposure in laboratory animal can lead to a variety of motor dysfunctions including increased locomotor activity, stereotypies, diminished or enhanced response times, and parkinsonian-like features. With the exception of psychomotor impairment and hyperkinesia, MA-induced movement disorders are not well documented in humans. This review attempts to draw parallels between the animal and human changes in basal ganglia neurochemistry associated with MA exposure and offers explanations for why a parkinsonian phenotype is not apparent among individuals who use and abuse MA. Significant differences in the expression of neurotoxicity and presence of multiple environmental and pharmacologic confounds may account for the lack of a parkinsonian phenotype in humans despite evidence of altered dopamine function.

Pharmacology, neurobiology and neurotoxicity of methamphetamine

“…Miller et al showed that toxic doses of MA increase the expression of GFAP in the striatum of the C57BL/6J mice [49]. Similar effects were seen in other brain regions including cerebellum and hippocampus [14,50]. Prolonged MA exposure causes neurotoxicity by apoptotic and neurotoxic mechanisms in striatal cells [10,51].…”

“…Studies have shown that alpha-methyl-tyrosine (AMT) attenuates, whereas reserpine potentiates the releasing action of AMP [27,28]. Acute and prolonged MA exposure can elevate postsynaptic nigrostriatal DA [14,22]. Acute MA administration can result in increased dopamine turnover in the caudate nucleus, and changes in monoamines and peptides in the basal ganglia [14,29,30].…”

“…Acute and prolonged MA exposure can elevate postsynaptic nigrostriatal DA [14,22]. Acute MA administration can result in increased dopamine turnover in the caudate nucleus, and changes in monoamines and peptides in the basal ganglia [14,29,30]. Acute administration of high and repeated doses of MA/AMP in monkeys, results in a transitory decline in DA in various brain regions.…”

Methamphetamine Addiction: A Review of the Literature

“…Parkinson's disease psychomotor disturbances have been reported among methamphetamine heavy users [61]. To confirm this hypothesis, a retrospective case-controlled study revealed that prolonged use of methamphetamine is associated with an eight-fold increased risk of Parkinson's disease with an average of 27 years between amphetamine exposure and the onset of signs [62].…”

Tardive dyskinesia on clozapine: A case report

“…Methamphetamine abuse has been implicated in the onset of hyperkinetic disorders including chorea. 8 One could further speculate on whether our patient developed tardive dyskinesia on the basis of exposure to fluoxetine.…”