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.

INVERNIZZI, R.W., PIERUCCI, M., CALCAGNO, E., DI GIOVANNI, G., DI MATTEO, V., BENIGNO, A., et al. (2007). Selective Activation of Serotonin2C Receptors Stimulates GABA-ergic Function in the Rat Substantia Nigra Pars Reticulata: A Combined in Vivo Electrophysiological and Neurochemical Study. NEUROSCIENCE, 144, 1523-1535 [10.1016/j.neuroscience.2006.11.004.].

Selective Activation of Serotonin2C Receptors Stimulates GABA-ergic Function in the Rat Substantia Nigra Pars Reticulata: A Combined in Vivo Electrophysiological and Neurochemical Study.

DI GIOVANNI, Giuseppe;BENIGNO, Arcangelo;
2007-01-01

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.
2007
INVERNIZZI, R.W., PIERUCCI, M., CALCAGNO, E., DI GIOVANNI, G., DI MATTEO, V., BENIGNO, A., et al. (2007). Selective Activation of Serotonin2C Receptors Stimulates GABA-ergic Function in the Rat Substantia Nigra Pars Reticulata: A Combined in Vivo Electrophysiological and Neurochemical Study. NEUROSCIENCE, 144, 1523-1535 [10.1016/j.neuroscience.2006.11.004.].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/17779
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