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Endocannabinoids regulate DA reward seeking

Contribution by NCA researchers Tommy Pattij and Dustin Schetters to a paper in Neuron

In cooperation with the research group of dr. Joseph Cheer (University of Maryland, Baltimore, USA), Tommy Pattij and Dustin Schetters (Dept. Anatomy and Neurosciences, VUmc) contribute to a Neuron paper. To assess whether endocannabinoids regulate reward seeking, in this paper by Oleson et al. endocannabinoid neurotransmission in the VTA was manipulated and found to alter cue-evoked dopamine levels in the NAc and reward seeking. These data suggest that endocannabinoid signaling in the VTA regulates reward seeking by sculpting dopamine release.

Endocannabinoids Shape Accumbal Encoding of Cue-Motivated Behavior via CB1 Receptor Activation in the Ventral Tegmentum

Transient increases in nucleus accumbens (NAc) dopamine concentration are observed when animals are presented with motivationally salient stimuli and are theorized to energize reward seeking. They arise from high-frequency firing of dopamine neurons in the ventral tegmental area (VTA), which also results in the release of endocannabinoids from dopamine cell bodies. In this context, endocannabinoids are thought to regulate reward seeking by modulating dopamine signaling, although a direct link has never been demonstrated. To test this, we pharmacologically manipulated endocannabinoid neurotransmission in the VTA while measuring transient changes in dopamine concentration in the NAc during reward seeking. Disrupting endocannabinoid signaling dramatically reduced, whereas augmenting levels of the endocannabinoid 2-arachidonoylglycerol (2AG) increased, cue-evoked dopamine concentrations and reward seeking. These data suggest that 2AG in the VTA regulates reward seeking by sculpting ethologically relevant patterns of dopamine release during reward-directed behavior.

Link to the paper: http://www.cell.com/neuron/abstract/S0896-6273(11)01096-8