Repeated amphetamine exposure altered reward-related brain responses in healthy volunteers while rewarded reaction times remained unchanged. Sensitization therefore did not produce a uniform increase in every measured response.
O’Daly and colleagues used a randomized double-blind parallel-group design to examine acute amphetamine effects following a sensitizing regimen. Participants completed a rewarded gambling task during functional MRI. The analysis separated decision-making, anticipation of reward and response to the outcome. This was controlled human exposure, not a clinical follow-up of people with long-standing dependence.
The study found evidence of sensitization to subjective drug effects. Brain findings depended on task phase: dorsal-striatal signal during decision-making decreased, ventromedial caudate activity during anticipation increased, and amygdala response to reward outcomes was blunted. Rewarded reaction times did not change. These directions cannot be combined into a claim of globally increased activation or uniformly improved reward processing.
The sample was relatively small, and blood-oxygenation signals are indirect measures of neural processes. The design did not directly measure neurotransmitter release in each highlighted region. A model intended to study mechanisms relevant to psychosis or addiction does not demonstrate that the volunteers developed those disorders. Nor does greater subjective sensitivity establish greater impairment on a particular task. The findings support examining prior exposure and the stage of reward processing when interpreting acute effects; they do not provide a diagnostic scan, a universal sensitization rule or a concentration-based impairment threshold.
See why regional imaging measurements require outcome-specific interpretation.