Selective activation of 5-HT2C receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: A combined in vivo electrophysiological and neurochemical study

R. W. Invernizzi, M. Pierucci, E. Calcagno, G. Di Giovanni, V. Di Matteo, A. Benigno, E. Esposito

Research output: Contribution to journalArticlepeer-review

Abstract

In vivo electrophysiology and microdialysis were used to investigate the physiological role of 5-HT2C receptors in the control of substantia nigra pars reticulata (SNr) function. Extracellular single-unit recordings were performed from putative GABA-containing neurons in the SNr of anesthetized rats, and local GABA release was studied by in vivo microdialysis in the SNr of awake freely-moving rats. Systemic administration of the selective 5-HT2C receptor agonist (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 (RO 60-0175) caused a dose-dependent excitation of about 30% of the SNr neurons recorded. However, the remaining neurons were either inhibited or unaffected by systemic RO 60-0175, in similar proportion. Local application of RO 60-0175 by microiontophoresis caused excitation in the majority of SNr neurons tested (48%), whereas a group of neurons was inhibited (16%) or unaffected (36%). Both the excitatory and the inhibitory effects of systemic and microiontophoretic RO 60-0175 were completely prevented by pretreatment with SB 243213 [5-methyl-1-({2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl}carbamoyl)-6-trifluo romethylindoline], a selective and potent 5-HT2C receptor antagonist. Consistent with these electrophysiological data, both systemic and intranigral administration of RO 60-0175 and m-chlorophenylpiperazine (mCPP), a non-selective 5-HT2C agonist, markedly increased extracellular GABA levels in the SNr. The stimulatory effect of systemic and local RO 60-0175 on GABA release was completely prevented by systemic administration of SB 243213, whereas local application of SB 243213 into the SNr only partially blocked RO 60-0175-induced GABA release. It is concluded that selective activation of 5-HT2C receptors stimulates GABA-ergic function in the SNr, and the clinical relevance of these data is discussed.

Original languageEnglish
Pages (from-to)1523-1535
Number of pages13
JournalNeuroscience
Volume144
Issue number4
DOIs
Publication statusPublished - Feb 23 2007

Keywords

  • 5-HT receptors
  • basal ganglia
  • electrophysiology
  • GABA
  • microdialysis
  • substantia nigra pars reticulata

ASJC Scopus subject areas

  • Neuroscience(all)

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