TY - JOUR T1 - Stimulation of Serotonin<sub>2C</sub> Receptors Blocks the Hyperactivation of Midbrain Dopamine Neurons Induced by Nicotine Administration JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 109 LP - 118 DO - 10.1124/jpet.103.062208 VL - 309 IS - 1 AU - Massimo Pierucci AU - Vincenzo Di Matteo AU - Ennio Esposito Y1 - 2004/04/01 UR - http://jpet.aspetjournals.org/content/309/1/109.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -