title: Leptin regulates dopamine responses to sustained stress in humans.
abstract: 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 [(11)C]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.
authors.affiliation: Molecular and Behavioral Neuroscience Institute, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109, USA. pburghar@umich.edu
authors.forename: Paul R
authors.initials: PR
authors.lastname: Burghardt
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Love
authors.forename: Christian S
authors.initials: CS
authors.lastname: Stohler
authors.forename: Colin
authors.initials: C
authors.lastname: Hodgkinson
authors.forename: Pei-Hong
authors.initials: PH
authors.lastname: Shen
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D004298:Dopamine / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008297:Male; D046228:Microarray Analysis; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000502:physiology; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000502:physiology; D010146:Pain / Q000503:physiopathology / Q000523:psychology; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D020891:Raclopride; D019275:Radiopharmaceuticals; D013315:Stress, Psychological / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D020738:Leptin; D019275:Radiopharmaceuticals; D020891:Raclopride; D004298:Dopamine