| Autor: |
INVERNIZZI, RW, PIERUCCI, M, CALCAGNO, E, DI MATTEO, V, ESPOSITO, E., DI GIOVANNI, Giuseppe, BENIGNO, Arcangelo |
| Přispěvatelé: |
INVERNIZZI, RW, PIERUCCI, M, CALCAGNO, E, DI GIOVANNI, G, DI MATTEO, V, BENIGNO, A, ESPOSITO, E |
| Jazyk: |
angličtina |
| Rok vydání: |
2007 |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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