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 fully generalized with an Effective Dose (ED)(50) of 0.005 mg/kg, s.c. A further selective 5-HT(2A) antagonist, SR46349, similarly generalized with an ED(50) of 0.04 mg/kg, s.c. In distinction, the selective 5-HT(2B) antagonist, SB204,741 (0.63 and 10.0 mg/kg), the 5-HT(2B/2C) antagonist, SB206,553 (0.16 and 2.5 mg/kg) and the selective 5-HT(2C) 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-HT(2A) receptors by MDL100,907 elicits a discriminative stimulus in rats which appears to be specifically mediated via 5-HT(2A) as compared with 5-HT(2B) and 5-HT(2C) receptors.
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