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Tiffany M. Love, BS; Christian S. Stohler, DMD; Jon-Kar Zubieta, MD, PhD

Arch Gen Psychiatry. 2009;66(10):1124-1134.

Context  The endogenous opioid system and opioid µ receptors (µ-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 µ-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 µ-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 µ-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 µ-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 µ-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 µ-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.

Author Affiliations: The Molecular & Behavioral Neuroscience Institute (Ms Love and Dr Zubieta) and Departments of Psychiatry and Radiology (Dr Zubieta), University of Michigan, Ann Arbor; and School of Dentistry, University of Maryland, Baltimore (Dr Stohler).

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