In vivo PET of cerebral cannabinoid-1 receptor availability is inversely correlated to novelty seeking in healthy human volunteers

Abstract

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Objectives: Neurochemistry may account for personality traits as a variance of behavioural patterns among individuals, as has been demonstrated for the dopamine and serotonin system by genetic and neuroimaging studies. The cerebral cannabinoid-1 receptor (CB1R) is an ubiquitous G-protein coupled receptor which presynaptically modulates other neurotransmitters. We have correlated regional CB1R availability, using a novel high-affinity and subtype-selective PET radioligand [¹⁸F]-MK9470. with the temperament dimensions of Cloninger's Temperament and Character Inventory (TCI). Methods: 47 healthy volunteers (23 M/24 F, age range 18-69 years) were investigated by [¹⁸F]-MK9470 PET. Parametric images of CB1R availability were determined by an area-under-the-curve model. Images were analyzed on a voxel-basis by statistical parametric mapping (SPM2). TCI scores (240 item) were normalized and converted into Z-scores as input for partial correlation calculations, correcting for age and gender effects. Results: Novelty seeking was inversely correlated to global CB1R availability (p=0.003, corrected for multiple comparisons). The subdimension “extravagance” showed a highly significant inverse correlation to CB1R availability (p<0.0001), especially in the amygdala, anterior cingulate, bilateral parietal cortex and precuneus. Also “disorderliness” was inversely correlated to global CB1R availability (p<0.0001). Conclusions: Low CB1R availability correlates to some items of the 240 item TCI personality scores. These findings suggest a potential role for the CB1R in behaviour. Further investigation of the relationships between the monoamine and cannabinoid systems may increase understanding of the neurochemical and neuroanatomical interactions that underlie these traits.

Research Support (if any): Research Council of the K.U.Leuven (OT/05/58), the Flemish Fund for Scientific Research (FWO/G.0548.06)