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Differential effects of the 5-HT2A receptor antagonist MDL100,907 and the 5-HT2C receptor antagonist SB242,084 on cocaine induced locomotor activity, cocaine self-administration and cocaine induced reinstatement of responding



Differential effects of the 5-HT2A receptor antagonist MDL100,907 and the 5-HT2C receptor antagonist SB242,084 on cocaine induced locomotor activity, cocaine self-administration and cocaine induced reinstatement of responding



Society for Neuroscience Abstracts 27(1): 1176



These studies investigated the effects of selective antagonists for the 5-HT2A, 5-HT2B and 5-HT2C receptors on the behavioural effects of cocaine. In the first series of experiments the 5-HT2A receptor antagonist M100,907 (0.5 mg/kg) attenuated locomotor activity elicited by 10 mg/kg cocaine. In contrast the 5-HT2C receptor antagonist SB242,084 (0.5 mg/kg) potentiated activity induced by cocaine. The 5-HT2B antagonist SB215,505 (3 mg/kg) did not alter cocaine-induced locomotor activity. In the second series of experiments the effects of M100,907 and SB242,084 were examined in rats self-administering cocaine on a progressive ratio schedule. At doses of 0.5, 1 and 2 mg/kg M100,907 did not alter responding for cocaine at an infusion dose of 0.25 mg. Similarly, M100,907 (0.5 mg/kg) failed to alter responding for cocaine at infusion doses of 0.0625, 0.125 and 0.25 mg. Responding for cocaine (0.125 mg) was increased by 0.5 and 1 mg/kg SB242,084. Examination of the effects of 0.5 mg/kg SB242,084 on the cocaine-dose response curve revealed increased responding for infusion doses of 0.0625 and 0.125 but not 0.25 mg or saline. After completion of these experiments lever-pressing was extinguished. M100,907 attenuated the ability of experimenter-administered cocaine to reinstate lever pressing, whereas the priming effect of cocaine was enhanced by SB242,084. These results indicate that 5-HT2A versus 5-HT2C receptor blockade generally exert opposing effects on cocaine mediated behavioural effects.

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