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The Journal of Neuroscience, December 31, 2008, 28(53):14372-14378; doi:10.1523/JNEUROSCI.2423-08.2008

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Behavioral/Systems/Cognitive
Midbrain Dopamine Receptor Availability Is Inversely Associated with Novelty-Seeking Traits in Humans

David H. Zald,1,2 Ronald L. Cowan,2,3 Patrizia Riccardi,4 Ronald M. Baldwin,3 M. Sib Ansari,3 Rui Li,3 Evan S. Shelby,1 Clarence E. Smith,3 Maureen McHugo,1 and Robert M. Kessler3

Departments of 1Psychology, 2Psychiatry, and 3Radiological Sciences, Vanderbilt University Nashville, Tennessee 37240, and 4Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, New York 10461

Correspondence should be addressed to Dr. David H. Zald, Department of Psychology, PMB 407817, 2301 Vanderbilt Place, Nashville, TN 37240. Email: david.zald{at}vanderbilt.edu

Novelty-seeking personality traits are a major risk factor for the development of drug abuse and other unsafe behaviors. Rodent models of temperament indicate that high novelty responding is associated with decreased inhibitory autoreceptor control of midbrain dopamine neurons. It has been speculated that individual differences in dopamine functioning also underlie the personality trait of novelty seeking in humans. However, differences in the dopamine system of rodents and humans, as well as the methods for assessing novelty responding/seeking across species leave unclear to what extent the animal models inform our understanding of human personality. In the present study we examined the correlation between novelty-seeking traits in humans and D2-like (D2/D3) receptor availability in the substantia nigra/ventral tegmental area. Based on the rodent literature we predicted that novelty seeking would be characterized by lowered levels of D2-like (auto)receptor availability in the midbrain. Thirty-four healthy adults (18 men, 16 women) completed the Tridimensional Personality Questionnaire-Novelty-Seeking Scale and PET scanning with the D2/D3 ligand [18F]fallypride. Novelty-Seeking personality traits were inversely associated with D2-like receptor availability in the ventral midbrain, an effect that remained significant after controlling for age. We speculate that the lower midbrain (auto)receptor availability seen in high novelty seekers leads to accentuated dopaminergic responses to novelty and other conditions that induce dopamine release.

Key words: autoreceptor; dopamine; D2; ventral tegmental area, substantia nigra; emotion; motivation; reward; personality

Received May 28, 2008; revised Oct. 14, 2008; accepted Nov. 5, 2008.

Correspondence should be addressed to Dr. David H. Zald, Department of Psychology, PMB 407817, 2301 Vanderbilt Place, Nashville, TN 37240. Email: david.zald{at}vanderbilt.edu






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