Amphetamine-induced dopamine release and post-synaptic specific binding in patients with mild tardive dyskinesia.
Several lines of evidence suggest that changes in dopamine release and/or post-synaptic sensitivity may be involved in the pathogenesis of tardive dyskinesia (TD). Preclinically, increased D(2) receptor sensitivity and dopamine turnover are associated with D(2) receptor antagonism. Clinically, development of TD is associated with D(2) receptor antagonist administration. Eight patients with mild evidence of TD (AIMS ratings > or =14) and six without (AIMS = 10), underwent [(11)C]raclopride PET scans. Baseline and amphetamine-induced decrements in striatal specific binding were assessed. Baseline and amphetamine-induced decrements in specific binding did not differ between patients with and without evidence of mild TD (p =.53). AIMS ratings did not significantly correlate with baseline (p =.76) or decrements in specific binding (p =.45). This study provides evidence that TD is not associated with increased amphetamine-induced presynaptic dopamine release and/or D(2) receptor binding as measured by [(11)C]raclopride PET. More research is needed to unravel the neurobiology of this debilitating disorder.
Adler
Caleb M
CM
Experimental Therapeutics Branch, National Institute of Mental Health/NIH, Bethesda, MD, USA.
Malhotra
Anil K
AK
Elman
Igor
I
Pickar
David
D
Breier
Alan
A
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D001665:Binding Sites / Q000187:drug effects; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D020891:Raclopride / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine