Aberrant mesolimbic dopamine-opiate interaction in obesity (2015)

Neuroimage. 2015 Aug 7. pii: S1053-8119(15)00709-0. doi: 10.1016/j.neuroimage.2015.08.001. [Epub ahead of print]

Tuominen L1, Tuulari J2, Karlsson H2, Hirvonen J2, Helin S2, Salminen P3, Parkkola R4, Hietala J5, Nuutila P2, Nummenmaa L6.


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 [11C]carfentanil and [11C]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.