Context: The endogenous opioid system and opioid mu receptors (mu-receptors) are known to interface environmental events, positive (eg, relevant emotional stimuli) and negative (eg, stressors), with pertinent behavioral responses and to regulate motivated behavior.

Objective: To examine the degree to which trait impulsiveness (the tendency to act on cravings and urges rather than to delay gratification) is predicted by baseline mu-receptor availability or the response of this system to a standardized, experientially matched stressor.

Design, setting, and patients: Nineteen young healthy male volunteers completed a personality questionnaire (NEO Personality Inventory, Revised) and underwent positron emission tomography scans with the mu-receptor-selective radiotracer carfentanil labeled with carbon 11. Measures of receptor concentrations were obtained at rest and during receipt of an experimentally maintained pain stressor of matched intensity between subjects.

Main outcome measures: Baseline receptor levels and stress-induced activation of mu-opioid system neurotransmission compared between subjects scoring above and below the population median on the NEO Personality Inventory, Revised, impulsiveness subscale and the orthogonal dimension (deliberation) expected to interact with it.

Results: High impulsiveness and low deliberation scores were associated with significantly higher regional mu-receptor concentrations and greater stress-induced endogenous opioid system activation. Effects were obtained in the prefrontal and orbitofrontal cortices, anterior cingulate, thalamus, nucleus accumbens, and basolateral amygdala-all regions involved in motivated behavior and the effects of drugs of abuse. Availability of the mu-receptor and the magnitude of stress-induced endogenous opioid activation in these regions accounted for 17% to 49% of the variance in these personality traits.

Conclusions: Individual differences in the function of the endogenous mu-receptor system predict personality traits that confer vulnerability to or resiliency against risky behaviors such as the predisposition to develop substance use disorders. These personality traits are also implicated in psychopathological states (eg, personality disorders) in which variations in the function of this neurotransmitter system also may play a role.