5-HT2c Receptors localize to dopamine and gaba neurons in the rat mesoaccumbens pathway

Marcy J. Bubar, Sonja J. Stutz, Kathryn Cunningham

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The serotonin 5-HT2C receptor (5-HT2CR) is localized to the limbic-corticostriatal circuit, which plays an integral role in mediating attention, motivation, cognition, and reward processes. The 5-HT2CR 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-HT2CR within dopamine VTA neurons suggesting the possibility of a direct influence of the 5-HT2CR 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-HT2CR 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-HT2CR immunoreactivity. Thus, we demonstrate for the first time that the 5-HT2CR 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-HT2CR 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.

Original languageEnglish (US)
Article numbere20508
JournalPLoS One
Volume6
Issue number6
DOIs
StatePublished - 2011

Fingerprint

Receptor, Serotonin, 5-HT2C
Ventral Tegmental Area
Dopaminergic Neurons
dopamine
gamma-aminobutyric acid
Neurons
Rats
Dopamine
gamma-Aminobutyric Acid
neurons
Nucleus Accumbens
receptors
rats
tyrosine 3-monooxygenase
immunochemistry
Aminobutyrates
Glutamate Decarboxylase
Tyrosine 3-Monooxygenase
Immunochemistry
GABAergic Neurons

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

5-HT2c Receptors localize to dopamine and gaba neurons in the rat mesoaccumbens pathway. / Bubar, Marcy J.; Stutz, Sonja J.; Cunningham, Kathryn.

In: PLoS One, Vol. 6, No. 6, e20508, 2011.

Research output: Contribution to journalArticle

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