Midbrain dopamine receptor availability is inversely associated with novelty-seeking traits in humans

Abstract

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 D(2)-like (D(2)/D(3)) 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 D(2)-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 D(2)/D(3) ligand [(18)F]fallypride. Novelty-Seeking personality traits were inversely associated with D(2)-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.

Figure 1.

[¹⁸F]Fallypride BP_ND in the DA midbrain of an individual subject. A, The two peaks (marked by arrows) correspond to the SN. Higher BP_ND levels can also be seen in the medial temporal lobe, and the basal forebrain. B, A blowup of the DA midbrain region in the same subject. Significant BP_ND levels can also be seen in the colliculus at the bottom of the figure. The color scale moves from purple (low: BP_ND ≥ 0.50), to yellow (high: BP_ND > 4.0).

Figure 2.

Inverse correlation between [¹⁸F]fallypride BP_ND in the DA midbrain and total Novelty-Seeking Score. A shows a sagittal slice through the right SN. B provides a scatter plot of each participant's Total Novelty Score and [¹⁸F]fallypride BP_ND at the peak coordinate. C displays a series of axial slices through the midbrain ranging from a z of −10 to −19. In A and C, the parametric maps were thresholded to only show voxels with correlations that exceed the p < 0.05 level (uncorrected) for magnitude, with areas in red exceeding r = −0.50. R, Right; L, left.

Figure 3.

Model of autoreceptor control and individual differences in novelty seeking. Because of their lower number of available somatodendritic autoreceptors, local somatodendritic release of DA in the SN/VTA produces less autoinhibition of DA cell firing in high novelty seekers relative to low novelty seekers. As a consequence, high novelty seekers release more DA in axon target regions when stimulated by novelty or other conditions that cause midbrain DA cells to fire.