ORIGINAL ARTICLES Amphetamine-Induced Dopamine Release in Human Ventral Striatum Correlates with Euphoria

Background: Studies in experimental animals have im-plicated the mesolimbic dopaminergic projections into the ventral striatum in the neural processes underlying behav-ioral reinforcement and motivated behavior; however, understanding the relationship between subjective emo-tional experience and ventral striatal dopamine (DA) release has awaited human studies. Using positron emis-sion tomography (PET), we correlated the change in endogenous dopamine concentrations following dextro-amphetamine (AMPH) administration with the associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions. Methods: We obtained PET measures of [11C]raclopride specific binding to DA D2/D3 receptors before and after AMPH injection (0.3 mg/kg IV) in seven healthy subjects. The change in [11C]raclopride binding potential (DBP) induced by AMPH pretreatment and the correlation be-tween DBP and the euphoric response to AMPH were compared between the anteroventral striatum (AVS; com-prised of accumbens area, ventromedial caudate, and anteroventral putamen) and the dorsal caudate (DCA) using an MRI-based region of interest analysis of the PET data. Results: The mean DBP was greater in the AVS than in the DCA (p,.05). The AMPH-induced changes in euphoria analog scale scores correlated inversely with DBP in the AVS (r 5 2.95; p,.001), but not in the DCA (r 5.30, ns). Post hoc assessments showed that changes in tension–anxiety ratings correlated positively with DBP in the AVS (r 5.80; p [uncorrected] ,.05) and that similar relationships may exist between DBP and emotion ratings in the ventral putamen (as were found in the AVS). Conclusions: The preferential sensitivity of the ventral striatum to the DA releasing effects of AMPH previously demonstrated in experimental animals extends to humans. The magnitude of ventral striatal DA release correlates positively with the hedonic response to AMPH. Bio