title: 5-HT(2C) receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway.
abstract: The serotonin 5-HT(2C) receptor (5-HT(2C)R) is localized to the limbic-corticostriatal circuit, which plays an integral role in mediating attention, motivation, cognition, and reward processes. The 5-HT(2C)R is linked to modulation of mesoaccumbens dopamine neurotransmission via an activation of γ-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA). However, we recently demonstrated the expression of the 5-HT(2C)R within dopamine VTA neurons suggesting the possibility of a direct influence of the 5-HT(2C)R upon mesoaccumbens dopamine output. Here, we employed double-label fluorescence immunochemistry with the synthetic enzymes for dopamine (tyrosine hydroxylase; TH) and GABA (glutamic acid decarboxylase isoform 67; GAD-67) and retrograde tract tracing with FluoroGold (FG) to uncover whether dopamine and GABA VTA neurons that possess 5-HT(2C)R innervate the nucleus accumbens (NAc). The highest numbers of FG-labeled cells were detected in the middle versus rostral and caudal levels of the VTA, and included a subset of TH- and GAD-67 immunoreactive cells, of which >50% also contained 5-HT(2C)R immunoreactivity. Thus, we demonstrate for the first time that the 5-HT(2C)R colocalizes in DA and GABA VTA neurons which project to the NAc, describe in detail the distribution of NAc-projecting GABA VTA neurons, and identify the colocalization of TH and GAD-67 in the same NAc-projecting VTA neurons. These data suggest that the 5-HT(2C)R may exert direct influence upon both dopamine and GABA VTA output to the NAc. Further, the indication that a proportion of NAc-projecting VTA neurons synthesize and potentially release both dopamine and GABA adds intriguing complexity to the framework of the VTA and its postulated neuroanatomical roles.
authors.affiliation: Department of Pharmacology and Toxicology and Center for Addiction Research, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Marcy J
authors.initials: MJ
authors.lastname: Bubar
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Stutz
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008297:Male; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology* / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D013194:Staining and Labeling; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D044405:Receptor, Serotonin, 5-HT2C; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; D004298:Dopamine