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Zaniewska M, McCreary AC, Wydra K, Filip M: Differential effects of serotonin (5-HT)(2) receptor-targeting ligands on locomotor responses to nicotine-repeated treatment. Synapse. 2010 Mar 1;64(7):511-519.
We verified the hypothesis that serotonin (5-HT)(2) receptors control the locomotor effects of nicotine (0.4 mg kg (-1)) in rats by using the 5-HT (2A) receptor antagonist M100907, the preferential 5-HT (2A) receptor agonist DOI, the 5-HT (2C) receptor antagonist SB 242084, and the 5-HT (2C) receptor agonists Ro 60-0175 and WAY 163909. Repeated pairings of a test environment with nicotine for 5 days, on Day 10 significantly augmented the locomotor activity following nicotine administration. Of the investigated 5-HT (2) receptor ligands, M100907 (2 mg kg (-1)) or DOI (1 mg kg (-1)) administered during the first 5 days in combination with nicotine attenuated or enhanced, respectively, the development of nicotine sensitization. Given acutely on Day 10, M100907 (2 mg kg (-1)), Ro 60-0175 (1 mg kg (-1)), and WAY 163909 (1.5 mg kg (-1)) decreased the expression of nicotine sensitization. In another set of experiments, where the nicotine challenge test was performed on Day 15 in animals treated repeatedly (Days: 1-5, 10) with nicotine, none of 5-HT (2) receptor ligands administered during the second withdrawal period (Days: 11-14) to nicotine-treated rats altered the sensitizing effect of nicotine given on Day 15. Our data indicate that 5-HT (2A) receptors (but not 5-HT (2C) receptors) play a permissive role in the sensitizing effects of nicotine, while stimulation of 5-HT (2A) receptors enhances the development of nicotine sensitization and activation of 5-HT (2C) receptors is essential for the expression of nicotine sensitization. Repeated treatment with the 5-HT (2) receptor ligands within the second nicotine withdrawal does not inhibit previously established sensitization. Synapse 64:511-519, 2010. (c) 2010 Wiley-Liss, Inc. |
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