Abstract
Pharmacotherapy with amphetamine is effective in the management of attention-deficit/hyperactivity disorder (ADHD), now recognized in adults as well as in children and adolescents. Here we demonstrate that amphetamine treatment, similar to that used clinically for adult ADHD, damages dopaminergic nerve endings in the striatum of adult nonhuman primates. Furthermore, plasma concentrations of amphetamine associated with dopaminergic neurotoxicity in nonhuman primates are on the order of those reported in young patients receiving amphetamine for the management of ADHD. These findings may have implications for the pathophysiology and treatment of ADHD. Further preclinical and clinical studies are needed to evaluate the dopaminergic neurotoxic potential of therapeutic doses of amphetamine in children as well as adults.
Footnotes
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This work was supported by United States Public Health Service Grants DA13946, DA017964, and HD050202.
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doi:10.1124/jpet.105.087916.
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ABBREVIATIONS: ADHD, attention-deficit/hyperactivity disorder; DOPAC, dihydroxyphenylacetic acid; DAT, dopamine transporter; VMAT2, vesicular monoamine transporter 2; GC/MS, gas chromatography/mass spectroscopy; PFPA, pentafluoropropionic acid; 5-HT, 5-hydroxytryptamine; 5-HIAA, 5-hydroxyindoleacetic acid; RTI-121, 3β-(4-[125I]iodophenyl)tropane-2β-carboxylic acid isopropyl ester; WIN 35,428, 3β-[4-flurorophenyl]-tropane-2β-carboxylic acid methyl ester tartrate; DTBZ, dihydrotetrabenazine; ANOVA, analysis of variance.
- Received May 26, 2005.
- Accepted July 12, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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