Do preclinical findings of methamphetamine-induced motor abnormalities translate to an observable clinical phenotype?
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.
Caligiuri
Michael P
MP
UCSD School of Medicine, Department of Psychiatry and Psychiatry Service, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. mcaligiuri@ucsd.edu
Buitenhuys
Casey
C
D019969:Amphetamine-Related Disorders / Q000503:physiopathology / Q000523:psychology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D015259:Dopamine Agents / Q000633:toxicity*; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid