title: Aberrant mesolimbic dopamine-opiate interaction in obesity.
abstract: Dopamine and opioid neurotransmitter systems share many functions such as regulation of reward and pleasure. μ-Opioid receptors (MOR) modulate the mesolimbic dopamine system in ventral tegmental area and striatum, key areas implicated in reward. We hypothesized that dopamine and opioid receptor availabilities correlate in vivo and that this correlation is altered in obesity, a disease with altered reward processing. Twenty lean females (mean BMI 22) and 25 non-binge eating morbidly obese females (mean BMI 41) underwent two positron emission tomography scans with [(11)C]carfentanil and [(11)C]raclopride to measure the MOR and dopamine D2 receptor (DRD2) availability, respectively. In lean subjects, the MOR and DRD2 availabilities were positively associated in the ventral striatum (r=0.62, p=0.003) and dorsal caudate nucleus (r=0.62, p=0.004). Moreover, DRD2 availability in the ventral striatum was associated with MOR availability in other regions of the reward circuitry, particularly in the ventral tegmental area. In morbidly obese subjects, this receptor interaction was significantly weaker in ventral striatum but unaltered in the caudate nucleus. Finally, the association between DRD2 availability in the ventral striatum and MOR availability in the ventral tegmental area was abolished in the morbidly obese. The study demonstrates a link between DRD2 and MOR availabilities in living human brain. This interaction is selectively disrupted in mesolimbic dopamine system in morbid obesity. We propose that interaction between the dopamine and opioid systems is a prerequisite for normal reward processing and that disrupted cross-talk may underlie altered reward processing in obesity.
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland; Department of Psychiatry, University of Turku, Kunnallissairaalantie 20, 20700 Turku, Finland. Electronic address: ljtuom@utu.fi.
authors.forename: Lauri
authors.initials: L
authors.lastname: Tuominen
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Jetro
authors.initials: J
authors.lastname: Tuulari
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Henry
authors.initials: H
authors.lastname: Karlsson
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Semi
authors.initials: S
authors.lastname: Helin
authors.affiliation: Department of Surgery, Turku University Hospital, 20520 Turku, Finland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Salminen
authors.affiliation: Department of Radiology, Turku University Hospital and Turku University, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Parkkola
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland; Department of Psychiatry, University of Turku, Kunnallissairaalantie 20, 20700 Turku, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.affiliation: Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland; Mind Brain Laboratory, Department of Biomedical Engineering and Computational Science (BECS), Aalto University School of Science, 00076 Aalto, Finland; Brain Research Unit (BRU), Low Temperature Laboratory, Aalto University School of Science, 00076 Aalto, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Nummenmaa
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism*; D020891:Raclopride / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012201:Reward; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D020891:Raclopride; C017114:carfentanil; D005283:Fentanyl
keywords: Dopamine; Interaction; Obesity; Opioid; PET