The D2 antagonist sulpiride modulates the neural processing of both rewarding and aversive stimuli in healthy volunteers

Abstract

Rationale: Animal studies indicate that dopamine pathways in the ventral striatum code for the motivational salience of both rewarding and aversive stimuli, but evidence for this mechanism in humans is less established. We have developed a functional magnetic resonance imaging (fMRI) model which permits examination of the neural processing of both rewarding and aversive stimuli.

Objectives: The aim of the study was to determine the effect of the dopamine receptor antagonist, sulpiride, on the neural processing of rewarding and aversive stimuli in healthy volunteers.

Methods: We studied 30 healthy participants who were randomly allocated to receive a single dose of sulpiride (400 mg) or placebo, in a double-blind, parallel-group design. We used fMRI to measure the neural response to rewarding (taste or sight of chocolate) and aversive stimuli (sight of mouldy strawberries or unpleasant strawberry taste) 4 h after drug treatment.

Results: Relative to placebo, sulpiride reduced blood oxygenation level-dependent responses to chocolate stimuli in the striatum (ventral striatum) and anterior cingulate cortex. Sulpiride also reduced lateral orbitofrontal cortex and insula activations to the taste and sight of the aversive condition.

Conclusions: These results suggest that acute dopamine receptor blockade modulates mesolimbic and mesocortical neural activations in response to both rewarding and aversive stimuli in healthy volunteers. This effect may be relevant to the effects of dopamine receptor antagonists in the treatment of psychosis and may also have implications for the possible antidepressant properties of sulpiride.

Fig. 1

a All chocolate stimuli (placebo vs. sulpiride): Axial, sagittal and coronal image of decreased ventral striatum in the sulpiride group compared to the placebo group, activations thresholded at p = 0.01 uncorrected and whole brain cluster-corrected (p < 0.05 FWE for multiple comparisons). b Contrast estimates for ventral striatum at 14 16 −2 for sulpiride and placebo

Fig. 2

a Chocolate in the mouth plus the sight of chocolate (sulpiride vs. placebo): Axial, sagittal and coronal image of decreased anterior cingulate cortex activation in the sulpiride group compared to the placebo group, activations thresholded at p = 0.05 uncorrected and whole brain cluster-corrected (p < 0.05 FWE for multiple comparisons). b Contrast estimates for anterior cingulate at 10 16 30 for sulpiride and placebo

Fig. 3

a All strawberry stimuli (placebo vs. sulpiride): Axial, sagittal and coronal image of decreased LOFC activation in the sulpiride group compared to the placebo group, activations thresholded at p = 0.05 uncorrected and whole brain cluster-corrected (p < 0.05 FWE for multiple comparisons). b Contrast estimates for LOFC at 34 32 −8 for sulpiride and placebo