The role of the neuropeptide PEN receptor, GPR83, in the reward pathway: Relationship to sex-differences. (October 2019)

• Record Type: Journal Article
• Authors: Fakira, Amanda K.; Peck, Emily G.; Liu, Yutong; Lueptow, Lindsay M.; Trimbake, Nikita A.; Han, Ming-Hu; Calipari, Erin S.; Devi, Lakshmi A.
• Is Part Of: Neuropharmacology. Volume 157(2019)
• Publication Date: 2019-10
• Subjects: GIR -- Morphine -- proSAAS -- Voltammetry -- Cholinergic interneurons -- Dopamine; CIN cholinergic interneuron -- NAc nucleus accumbens -- VTA ventral tegmental area -- CPP conditioned place preference -- FSCV fast scanning cyclic voltammetry -- MSN medium spiny neuron -- DARPP-32 dopamine- and cAMP-regulated phosphoprotein -- nACh nicotinic acetyl choline receptor -- MEC mecamylamin; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107666
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: GPR83, the receptor for the neuropeptide PEN, exhibits high expression in the nucleus accumbens of the human and rodent brain, suggesting that it plays a role in modulating the mesolimbic reward pathway. However, the cell-type specific expression of GPR83, its functional impact in the reward pathway, and in drug reward-learning has not been fully explored. Using GPR83/eGFP mice, we show high GPR83 expression on cholinergic interneurons in the nucleus accumbens and moderate expression on ventral tegmental area dopamine neurons. In GPR83 knockout mice, baseline dopamine release in the nucleus accumbens is enhanced which disrupts the ratio of tonic vs phasic release. Additionally, GPR83 knockout leads to changes in the expression of dopamine-related genes. Using the morphine conditioned place preference model, we identify sex differences in morphine reward-learning, show that GPR83 is upregulated in the nucleus accumbens following morphine conditioned place preference, and show that shRNA-mediated knockdown of GPR83 in the nucleus accumbens leads to attenuation morphine reward. Together, these findings detect GPR83 expression in the reward-pathway, and show its involvement in dopamine release and morphine reward-learning. Highlights: GPR83 is expressed on cholinergic interneurons in the NAc and dopamine neurons in the VTA. Dopamine release in NAc slices is enhanced in GPR83 KO mice. Morphine-reward learning upregulates GPR83 expression in the NAc while GPR83 knockdown attenuates reward-learning. There are sex differences in morphine reward-learning.