The selective serotonin2A receptor antagonist, MDL100,907, elicits a specific interoceptive cue in rats

Employing, a two-lever, food-reinforced, Fixed Ratio 10 drug discrimination procedure, rats were trained to recognize the highly-selective serotonin (5-HT)(2A) receptor antagonist, MDL100,907 (0.16 mg/kg, i.p.). They attained criterion after a mean +/- S.E.M. of 70 +/- 11 sessions. MDL100,907 fullly generalized with an Effective Dose (ED)(50) of 0.005 mg/kg, s.c.. A further selective 5-HT2A antagonist, SR46349, similarly generalized with an (ED50) of anta 0 0.04 mg/kg, s.c. In distinction, the selective 5-HT2B antagonist, SB204,741 (0.63 and 10.0 mg/kg), the 5-HT2B/2C antagonist, SB206,553 (0.16 and 2.5 mg/kg) and the selective 5-HT2C antagonists, SB242,084 (2.5 and 10.0 mg/kg,) and RS102221 (2.5 and 10,0 mg/kg), did not significantly generalize. In conclusion, selective blockade of 5-HY2A receptors by MDL100,907 elicits a discriminative stimulus in rats which appears to be specifically mediated via 5-HT2A as compared with 5-HT,B and 5-HT2c receptors. (C) 2002 American College of Neuropsychopharmacology Published by Elsevier Science Inc.