Regulation of novelty seeking by midbrain dopamine D2/D3 signaling and ghrelin is altered in obesity


  • Funding agencies: This study was supported by National Institutes of Health (NIH) grants UL1-RR-024975 from the National Center for Research Resources (Vanderbilt Clinical and Translational Science Award), DK-20593 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; Vanderbilt Diabetes Research and Training Award), DK-058404 from NIDDK (Vanderbilt Digestive Disease Research Center), K12- ESO15855 from the National Institute of Environmental Health Sciences (Vanderbilt Environmental Health Science Scholars Program) to J.P.D., and DK-70860 from the NIDDK to N.N.A.

  • Disclosure: The authors have no competing interests.

  • Author contributions: J.P.D., D.H.Z. and N.N.A conceived of experiences and J.P.D. and N.N.A obtained funding. J.P.D., S.W.S., R.M.K., R.L.C., and P.M.S. carried out experiments. J.P.D. oversaw all experiments and data analysis. All authors were involved in writing the paper and had final approval of the submitted and published versions.



To investigate the relationship of novelty seeking traits (NS) with midbrain dopamine (DA) receptors and acyl ghrelin levels (AG) in normal weight (NW) and obese females.NS predict addictive behaviors and are hypothesized to contribute to eating behaviors. In healthy, NS are negatively associated with DA receptors in the substantia nigra (SN). The influence of obesity on the regulation of NS by DA signaling and AG was hypothesized.


PET scanning to measure DA type 2/type 3 receptor (D2/D3R) binding potential (BPND) in the SN was used. Participants completed Tridimensional Personality Questionnaire-Novelty-Seeking Scale (TPQ-NS) and AG were measured.


In eight NW and 19 obese (BMI 22 vs 38 kg/m2), TPQ-NS (16 vs 15) and SN D2/D3R BPND (2.48 vs 2.66) were similar, while AG higher (256 vs 60, P < 0.01), respectively. D2/D3R BPND and TPQ-NS had a negative relationship in NW (r = −0.7) but not in obese (P > 0.10). AG and TPQ-NS were positively correlated in NW (r = 0.9) but not in obese (P > 0.10). D2R BPND and AG were negatively correlated in NW (r = −0.8) but positively in obese (r = 0.6).


Obese do not maintain posited regulatory relationships for NS to either midbrain D2/D3R availability or AG present in NW. Also opposite relationships exist for NW and obese between SN D2/D3R availability and AG. The altered regulation of NS in obesity needs to be further explored.