Effects of methamphetamine on two measures of reward: Euphoria and neural activation to reward cues

Stimulants enhance dopamine function, affecting diverse aspects of reward function from neural processing of reward cues to feelings of well-being in humans. However, little is known about the relationships among different measures of reward function. Understanding relationships among different indices of reward processing could provide insight into the processes that control motivated behavior. The present study examined the effects of a single dose of methamphetamine on two measures of reward in healthy adults: feelings of well-being and neural activation with reward-related stimuli. In a randomized, within-subject, double-blind study, 88 healthy men and women received a single 20 mg oral dose of methamphetamine (MA) and placebo, across two sessions. Regional activations to reward-related cues were assessed using fMRI during the Monetary Incentive Delay task, and positive subjective effects of MA were assessed using standardized questionnaires. As expected, MA increased euphoria and feelings of well-being. MA had minimal effects on neural activation during either anticipation or receipt of reward, but it significantly increased ventral striatal activation during anticipation of monetary loss, suggesting heightened salience of loss-related cues. As reported previously, caudate activation during reward anticipation during the non-drug (placebo) session was correlated with euphoria induced by MA (on the MA session). However, this correlation between cue-induced neural activation and euphoria was not apparent on the MA session. Thus, MA-induced euphoria was related to reward cue-elicited neural activation only when participants were tested without the drug. MA increased neural reactivity to loss, and this was not correlated with euphoria. These findings suggest that MA can dampen reward-related neural activity normally detected in the drug-free state, and that it enhances brain responses to loss. Further research is needed to determine how neural responses to reward or loss cues are related to feelings of well-being, and how either of these affect reward-related behavior.