Changes in striatal D-2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates

Recent brain imaging studies suggest that schizophrenia may be related to a bnormally high amphetamine-induced dopamine release. It is known that repea ted use of amphetamine may cause paranoid psychosis and persisting stereoty pies. The biochemical background for these signs and symptoms has not been clarified. In this study, positron emission tomography and [C-11]raclopride were used to determine central D-2-dopamine receptor density (B-max) and a pparent affinity (K-D(app)) in Cynomolgus monkeys before and after 14 days of treatment with d-amphetamine sulphate (2 mg/kg/day; s.c.). One day after withdrawal from amphetamine, K-D(app) was increased, suggesting [C-11]racl opride competition with elevated concentration of dopamine. At 7 and 14 day s after withdrawal, there was a 19-26% decrease in B-max but no change in K -D(app) as compared to baseline. Although this study was performed on two m onkeys only, there was thus no support for the view that chronic intermitte nt hyperactivity of the dopamine system may be related to an upregulation o f striatal D-2-dopamine receptors. Repeated administration of amphetamine m ay, rather, cause a long-lasting downregulation of the D-2-receptor density , which may be a neurochemical correlate to the abnormal movements, anhedon ia, anxiety, and depression seen in psychostimulant abusers. Synapse 31:154 -162, 1999, (C) 1999 Wiley-Liss, Inc.