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, understanding the relationship between subjective emotional experience and ventral 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 associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions.


METHODS
We obtained PET measures of [(11)C]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 [(11)C]raclopride binding potential (DeltaBP) induced by AMPH pretreatment and the correlation between DeltaBP 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 interest analysis of the PET data.


RESULTS
The mean DeltaBP was greater in the AVS than in the DCA (p <.05). The AMPH-induced changes in euphoria analog scale scores correlated inversely with DeltaBP in the AVS (r = -.95; p <.001), but not in the DCA (r =.30, ns). Post hoc assessments showed that changes in tension-anxiety ratings correlated positively with DeltaBP in the AVS (r =.80; p [uncorrected] <.05) and that similar relationships may exist between DeltaBP 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.
Drevets
W C
WC
University of Pittsburgh School of Medicine, Department of Psychiatry, Medical Center, PET Facility Room B-938 PUH, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Gautier
C
C
Price
J C
JC
Kupfer
D J
DJ
Kinahan
P E
PE
Grace
A A
AA
Price
J L
JL
Mathis
C A
CA
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005059:Euphoria / Q000187:drug effects*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D018765:Dopamine Uptake Inhibitors; D000661:Amphetamine; D004298:Dopamine