Serotonin-2C receptor agonists decrease potassium-stimulated GABA release in the nucleus accumbens

James Kasper, Raymond G. Booth, Joanna Peris

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The serotonin 5-HT2C receptor has shown promise in vivo as a pharmacotherapeutic target for alcoholism. For example, recently, a novel 4-phenyl-2-N,N-dimethylaminotetralin (PAT) drug candidate, that demonstrates 5-HT2C receptor agonist activity together with 5-HT2A/2B receptor inverse agonist activity, was shown to reduce operant responding for ethanol after peripheral administration to rats. Previous studies have shown that the 5-HT2C receptor is found throughout the mesoaccumbens pathway and that 5-HT2C receptor agonism causes activation of ventral tegmental area (VTA) GABA neurons. It is unknown what effect 5-HT2C receptor modulation has on GABA release in the nucleus accumbens core (NAcc). To this end, microdialysis coupled to capillary electrophoresis with laser-induced fluorescence was used to quantify extracellular neurotransmitter concentrations in the NAcc under basal and after potassium stimulation conditions, in response to PAT analogs and other 5-HT2C receptor modulators administered by reverse dialysis to rats. 5-HT2C receptor agonists specifically attenuated stimulated GABA release in the NAcc while 5-HT2C antagonists or inverse agonists had no effect. Agents with activity at 5-HT2A receptors had no effect on GABA release. Thus, in contrast to results reported for the VTA, current results suggest 5-HT2C receptor agonists decrease stimulated GABA release in the NAcc, and provide a possible mechanism of action for 5HT2C-mediated negative modulation of ethanol self-administration.

Original languageEnglish (US)
Pages (from-to)78-85
Number of pages8
JournalSynapse
Volume69
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Receptor, Serotonin, 5-HT2C
Serotonin Receptor Agonists
Nucleus Accumbens
gamma-Aminobutyric Acid
Potassium
Serotonin 5-HT2 Receptor Agonists
Receptor, Serotonin, 5-HT2A
Ventral Tegmental Area
Ethanol
Serotonin 5-HT2 Receptor Antagonists
GABAergic Neurons
Self Administration
Microdialysis
Capillary Electrophoresis
Alcoholism
Neurotransmitter Agents
Dialysis
Lasers
Fluorescence

Keywords

  • 5-HT receptor
  • Capillary electrophoresis
  • GABA
  • Microdialysis
  • Nucleus accumbens

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Serotonin-2C receptor agonists decrease potassium-stimulated GABA release in the nucleus accumbens. / Kasper, James; Booth, Raymond G.; Peris, Joanna.

In: Synapse, Vol. 69, No. 2, 01.02.2015, p. 78-85.

Research output: Contribution to journalArticle

Kasper, James ; Booth, Raymond G. ; Peris, Joanna. / Serotonin-2C receptor agonists decrease potassium-stimulated GABA release in the nucleus accumbens. In: Synapse. 2015 ; Vol. 69, No. 2. pp. 78-85.
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