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Research ArticleNEUROPHARMACOLOGY

Stimulation of Serotonin2C Receptors Blocks the Hyperactivation of Midbrain Dopamine Neurons Induced by Nicotine Administration

Massimo Pierucci, Vincenzo Di Matteo and Ennio Esposito
Journal of Pharmacology and Experimental Therapeutics April 2004, 309 (1) 109-118; DOI: https://doi.org/10.1124/jpet.103.062208
Massimo Pierucci
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Vincenzo Di Matteo
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Ennio Esposito
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Abstract

In vivo electrophysiological techniques were used to study the effect of nicotine on the basal activity of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) of chloral hydrate-anesthetized rats. Acute i.v. injections of nicotine (25–400 μg/kg) caused a dose-dependent increase of the firing rate and the bursting activity of DA neurons both in the SNc and the VTA. Repeated daily injection of nicotine (1 mg/kg i.p.) for 10 consecutive days did not cause any significant change in the basal activity of DA neurons in the SNc and the VTA. Acute challenge with nicotine (25–400 μg/kg i.v.) in animals treated repeatedly with this drug caused a dose-related excitation of DA neurons in both areas. To test the hypothesis that stimulation of 5-hydroxytryptamine (5-HT, serotonin)2C receptors could affect nicotine-induced stimulation of DA neuronal activity, the selective 5-HT2C receptor agonist RO 60-0175 was used. Pretreatment with 100 μg/kg i.v. (S)-2-(chloro-5-fluoro-indo-l-yl)-l-methylethylamine 1:1 C4H4O4 (RO 60-0175) prevented the enhancement in DA neuronal firing rate elicited by acute nicotine (25–400 μg/kg i.v.) in the SNc of both drug naive and chronically treated rats but was devoid of any significant effect in the VTA. Moreover, the dose of 300 μg/kg i.v. RO 60-0175 significantly reduced the stimulatory effect of VTA DA neurons induced by acute challenge with nicotine (25–400 μg/kg i.v.) both in drug naive and chronically treated rats. It is concluded that selective activation of 5-HT2C receptors can block the stimulatory action of nicotine on midbrain DA neuronal activity.

Footnotes

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.103.062208.

  • ABBREVIATIONS: DA, dopamine; SNc, substantia nigra pars compacta; VTA, ventral tegmental area; 5-HT, 5-hydroxytryptamine, serotonin; RO 60-0175, (S)-2-(chloro-5-fluoro-indo-l-yl)-l-methylethylamine 1:1 C4H4O4; SB 242084, 6-chloro-5-methyl-l-[2-(2-methylpyridiyl-3-oxy)-pyrid-5-yl carbomoyl] indoline; ANOVA, analysis of variance.

    • Received October 30, 2003.
    • Accepted December 18, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 309 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 309, Issue 1
1 Apr 2004
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Research ArticleNEUROPHARMACOLOGY

Stimulation of Serotonin2C Receptors Blocks the Hyperactivation of Midbrain Dopamine Neurons Induced by Nicotine Administration

Massimo Pierucci, Vincenzo Di Matteo and Ennio Esposito
Journal of Pharmacology and Experimental Therapeutics April 1, 2004, 309 (1) 109-118; DOI: https://doi.org/10.1124/jpet.103.062208

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Research ArticleNEUROPHARMACOLOGY

Stimulation of Serotonin2C Receptors Blocks the Hyperactivation of Midbrain Dopamine Neurons Induced by Nicotine Administration

Massimo Pierucci, Vincenzo Di Matteo and Ennio Esposito
Journal of Pharmacology and Experimental Therapeutics April 1, 2004, 309 (1) 109-118; DOI: https://doi.org/10.1124/jpet.103.062208
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