Transient receptor potential vanilloid 3 (TRPV3) in the ventral tegmental area of rat: Role in modulation of the mesolimbic-dopamine reward pathway

Abstract

While dopamine (DA) neurons in the ventral tegmental area (VTA) drive the mesolimbic-reward pathway, confluent lines of evidence underscore the importance of transient receptor potential vanilloid (TRPV) channels as novel regulators of these neurons. Among the TRPV-subfamily, TRPV3 is of particular interest in reward, since active ingredients of flavour-enhancing spices in food serve as TRPV3 agonists and modulate DAergic neurotransmission. The nature of TRPV3 elements in the VTA and their role in driving the mesolimbic-DA-reward pathway has however, remained unexplored. We observed TRPV3 mRNA as well as TRPV3-immunoreactive neurons in the VTA of Wistar rats. We therefore explored whether these ion channels participate in modulating mesolimbic-DA reward pathway. In the posterior VTA (pVTA), 82 ± 2.6% of the TRPV3 neurons co-express tyrosine hydroxylase and 68 ± 5.5% of these neurons project to the nucleus accumbens shell (Acb shell). While ex vivo treatment of midbrain slices with TRPV3-agonist, thymol increased [Ca(2+)]i-activity in pVTA neurons, intra-pVTA injections of thymol in freely-moving, satiated rats enhanced positive reinforcement for active lever pressings in an operant chamber to self-administer sweet pellets. This behavior was attenuated by prior treatment with intra-Acb shell DA D1- and D2-like receptor antagonists. These results demonstrate a role for TRPV3 in driving mesolimbic-DA food-reward pathway, and underscores the importance of these channels in the VTA as key components processing reward.

Keywords: Dopamine; Mesolimbic-reward pathway; Reward; TRPV3 ion channels; Ventral tegmental area.