Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria

Background: Studies in experimental animals have implicated the mesolimbic dopaminergic projections into the ventral striatum in the neural processes underlying behavioral reinforcement and motivated behavior; however, unders tanding the relationship between subjective emotional experience and ventra l striatal dopamine (DA) release has awaited human studies. Using positron emission tomography (PET), we correlated the change in endogenous dopamine concentrations following dextroamphetamine (AMPH) administration with the a ssociated hedonic response in human subjects and compared the strength of t his correlation across striatal subregions, Methods: We obtained PET measures of [C-11]raclopride specific binding to D A D2/D3 receptors before and after AMPH injection (0.3 mg/kg IV) in seven h ealthy subjects. The change in [C-11]raclopride binding potential (Delta BP ) induced by AMPH pretreatment and the correlation between Delta BP and the euphoric response to AMPH were compared between the anteroventral striatum (AVS; comprised of accumbens area, ventromedial caudate, and anteroventral putamen) and the dorsal caudate (DCA) using an MRI-based region of interes t analysis of the PET data. Results: The mean Delta BP was greater in the AVS than in the DCA (p < .05) . The AMPH-induced changes in euphoria analog scale scores correlated inver sely with <Delta>BP in the AVS (r = -.95; p < .001), but not in the DCA (r = .30, ns). Post hoc assessments showed that changes in tension-anxiety rat ings correlated positively with <Delta>BP in the AVS (r = .80; p [uncorrect ed] < .05) and that similar relationships may exist between <Delta>BP and e motion 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. (C) 2001 Society of Biologica l Psychiatry.