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Interactions of serotonin (5‐HT) 2 receptor‐targeting ligands and nicotine: Locomotor activity studies in rats
Author(s) -
Zaniewska Magdalena,
McCreary Andrew C.,
Filip Małgorzata
Publication year - 2009
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20645
Subject(s) - nicotine , chemistry , 5 ht receptor , agonist , serotonin , antagonist , receptor , receptor antagonist , pharmacology , endocrinology , medicine , biochemistry
Male Wistar rats were used to verify the hypothesis that serotonin (5‐HT) 2A or 5‐HT 2C receptors may control the locomotor effects evoked by nicotine (0.4mg/kg). The 5‐HT 2A receptor antagonist (M100,907), the 5‐HT 2A receptor agonist (DOI), the 5‐HT 2C receptor antagonist (SB 242,084), and the 5‐HT 2C receptor agonists (Ro 60‐0175 and WAY 163,909) were used. M100,907 (0.5–2mg/kg) did not alter, while DOI (1 mg/kg) enhanced the nicotine‐induced hyperlocomotion. The effect of DOI was antagonized by M100,907 (1 mg/kg). SB 242,084 (0.25–1 mg/kg) augmented, while Ro 60‐0175 (1 and 3 mg/kg) and WAY 163,909 (1.5 mg/kg) decreased the overall effect of acute nicotine; effects of Ro 60‐0175 and WAY 163,909 were attenuated by SB 242,084 (0.125 mg/kg). In another set of experiments, M100,907 (2 mg/kg) on Day 10 attenuated, while DOI (0.1–1 mg/kg) enhanced the nicotine‐evoked conditioned hyperlocomotion in rats repeatedly (Days 1–5) treated with nicotine in experimental chambers. SB 242,084 (0.125 or 1 mg/kg) did not change, while Ro 60‐0175 (1 mg/kg) or WAY 163,909 (1.5 mg/kg) decreased the expression of nicotine‐induced conditioned hyperactivity. Only DOI (0.3 and 1 mg/kg) and SB 242,084 (1 mg/kg) enhanced the basal locomotion. The present data indicate that 5‐HT 2A receptors are significant for the expression of nicotine‐evoked conditioned hyperactivity. Conversely, 5‐HT 2C receptors play a pivotal role in the acute effects of nicotine. Pharmacological stimulation of 5‐HT 2A receptors enhances the conditioned hyperlocomotion, while activation of 5‐HT 2C receptors decreases both the response to acute nicotine and conditioned hyperactivity. Synapse 63:653–661, 2009. © 2009 Wiley‐Liss, Inc.