title: 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.
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, 752050, Odisha, India.
authors.forename: Uday
authors.initials: U
authors.lastname: Singh
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, 752050, Odisha, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, 440033, Maharashtra, India.
authors.forename: Gajanan P
authors.initials: GP
authors.lastname: Shelkar
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, 752050, Odisha, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Yadav
authors.affiliation: Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, 440033, Maharashtra, India.
authors.forename: Dadasaheb M
authors.initials: DM
authors.lastname: Kokare
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, 752050, Odisha, India.
authors.forename: Chandan
authors.initials: C
authors.lastname: Goswami
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Tupper Research Institute, Tufts Medical Center, Boston, MA, USA; Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lechan
authors.affiliation: School of Biological Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, 752050, Odisha, India. Electronic address: pssingru@niser.ac.in.
authors.forename: Praful S
authors.initials: PS
authors.lastname: Singru
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002460:Cell Line; D002491:Central Nervous System Agents / Q000494:pharmacology; D019422:Dietary Sucrose; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011897:Random Allocation; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism; D012201:Reward; D012646:Self Administration; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*; D013943:Thymol / Q000494:pharmacology; D046509:Tissue Culture Techniques; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D002491:Central Nervous System Agents; D019422:Dietary Sucrose; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D050916:TRPV Cation Channels; C505767:TRPV3 protein, rat; D013943:Thymol; D002118:Calcium; D004298:Dopamine
keywords: Dopamine; Mesolimbic-reward pathway; Reward; TRPV3 ion channels; Ventral tegmental area