PT  - JOURNAL ARTICLE
AU  - Paul R. Burghardt
AU  - Tiffany M. Love
AU  - Christian S. Stohler
AU  - Colin Hodgkinson
AU  - Pei-Hong Shen
AU  - Mary-Anne Enoch
AU  - David Goldman
AU  - Jon-Kar Zubieta
TI  - Leptin Regulates Dopamine Responses to Sustained Stress in Humans
AID  - 10.1523/JNEUROSCI.2521-12.2012
DP  - 2012 Oct 31
TA  - The Journal of Neuroscience
PG  - 15369--15376
VI  - 32
IP  - 44
4099  - http://www.jneurosci.org/content/32/44/15369.short
4100  - http://www.jneurosci.org/content/32/44/15369.full
SO  - J. Neurosci.2012 Oct 31; 32
AB  - Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [11C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.