m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat substantia nigra and ventral tegmental area by activating serotonin-2C receptors.
In vivo electrophysiological techniques were used to study the effect of m-chlorophenylpiperazine, a non-selective serotonin-2C receptor agonist, on the activity of non-dopaminergic neurons in the substantia nigra pars reticulata and the ventral tegmental area of anesthetized rats. Intravenous administration of m-chlorophenylpiperazine (5-320 microg/kg) caused a dose-dependent increase in the basal firing rate of a subpopulation of nigral neurons which do not respond to a footpinch stimulus [P(0) neurons], whereas it did not affect the activity of neurons which are responsive to the footpinch [P(+) neurons]. However, m-chlorophenylpiperazine (5-320 microg/kg) excited all non-dopaminergic neurons sampled in the ventral tegmental area. Moreover, microiontophoretic application of m-chlorophenylpiperazine (10-40 nA) caused an excitation of P(0) nigral and ventral tegmental area neurons. Pretreatment with the selective serotonin-2C receptor antagonist SB 242084 (200 microg/kg, i.v.) completely blocked the excitatory effect of i.v. m-chlorophenylpiperazine (5-320 microg/kg), both in the substantia nigra pars reticulata and in the ventral tegmental area. It is concluded that stimulation of serotonin-2C receptors by m-chlorophenylpiperazine activates non-dopaminergic (presumably GABA-containing) neurons in the substantia nigra pars reticulata and ventral tegmental area.
Di Giovanni
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G
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (Chieti), Italy.
Di Matteo
V
V
La Grutta
V
V
Esposito
E
E
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013378:Substantia Nigra / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005680:gamma-Aminobutyric Acid; C015068:1-(3-chlorophenyl)piperazine