Brain Function in Response to Motivational Stimuli

The purpose of this protocol is to advance the understanding of the behavioral neurobiology underlying substance dependency by exploring regional brain activity in response to appetitive and aversive stimuli in human subjects. In this protocol, brain activation is the dependent measure, as measured by blood oxygenation level dependent (BOLD) signal acquired during functional magnetic resonance (fMRI) imaging. Previous work in this laboratory has found that cues of anticipated monetary reward versus threat of negative reinforcement causes increased BOLD signal in the nucleus accumbens (NAcc) and other parts of the ventral striatum. This protocol is intended to extend these findings by exploring whether the recently reported BOLD activation (a hemodynamic response) in certain brain regions in response to motivational cues can be perturbed by dopaminergic pharmacological manipulations. In a series of two, repeated-measures, within-subject experiments, we propose to temporarily alter subjects' brain monoamine neurotransmitter systems with pharmacological interventions prior to presenting the subjects with appetitive and aversive visual stimuli as well as cues signaling potential punishment and reward. In the first experiment, brain catecholamine systems will be deactivated by dietary restrictions of amino acid precursors Tyrosine (Tyr) and Phenylalanine (Phe), respectively. In the second experiment, the brain dopamine (DA) release will be transiently increased with administration of dextroamphetamine (Amph). Based on a wealth of existent findings, we predict that acutely enhancing synaptic DA by Amph will augment reward-elicited activation in the ventral striatum. Conversely, acute dietary restriction of the DA precursor Tyr, (along with Tyr precursor Phe) will blunt this activation. Since substance use disorders (SUD) such as alcoholism may result from disordered neural systems regulating approach and avoidance behavior (with respect to the substance), this experiment can yield useful knowledge relevant to SUD.