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Original Article |
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Neuropsychopharmacology (2001) 25 642-650.10.1038/S0893-133X(01)00263-9
Subjective Effects of AMPT-induced Dopamine Depletion in Schizophrenia: Correlation between Dysphoric Responses and Striatal D2 Binding Ratios on SPECT Imaging
Lakshmi Voruganti1,2 MD, MSc, Piotr Slomka3 Ph.D, Pamela Zabel3 MSc, Giuseppe Costa2 BSc, Aaron So3 BSc, Adel Mattar3 MD and A George Awad1 MD, Ph.D |
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1Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
2Department of Psychiatry University of Western Ontario, London, Ontario, Canada
3Department of Nuclear Medicine, University of Western Ontario, London, Ontario, Canada
Correspondence: Dr Lakshmi Voruganti, Schizophrenia Treatment and Research (STAR) Program, 850 Highbury Avenue, London, ON N6A 4H1, Canada, Tel.: 519-455-5110 x 2533; Fax: 519-455-2677, E-mail: lvorugan@julian.uwo.ca
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ABSTRACT
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Approximately one third of schizophrenic patients treated with neuroleptic drugs experience unpleasant subjective responses, that are collectively known as neuroleptic dysphoria. Experimental research in animals indicates that drug induced dopaminergic blockade in mesolimbic circuits, especially the nucleus accumbens, leads to impaired pleasure responsivity and dysphoria. The present study tested this putative mechanism in drug-free schizophrenic patients (n = 12), through inducing dysphoric responses with alphamethyl paratyrosine (AMPT) and simultaneously quantifying their baseline striatal dopmine (D2) function with 123IBZM-SPECT imaging. Results showed a wide variability in the occurrence and severity of dysphoric responses, clearly distinguishing a dysphoric group from non-dysphoric responders. Severity of dysphoric responses, measured by standardized rating scales, correlated inversely with changes in D2 receptor binding ratios (r = +0.82, p < .01). These results support the notion that striatal dopaminergic activity is not uniformly elevated in all schizophrenic patients, and the sub-group of individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic blocking drugs.
Keywords: Dysphoria; Dopamine; Schizophrenia; Antipsychotic drugs |
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