Cyproheptadine prevents the initial occurrence of successive negative contrast.

Rats shifted from 32% to 4% sucrose make fewer licks for 4% sucrose than rats having only experienced the lower reward. In Experiment 1, the occurrence of this contrast effect was prevented by the administration of the nonspecific serotonin antagonist cyproheptadine (3.0 or 6.0 mg/kg). These results of Experiments 2 and 3 demonstrated that the contrast-reducing action of cyproheptadine was not mediated by the antiserotonergic properties of the drug since systemic administration of the serotonin synthesis inhibitor, PCPA (150 or 300 mg/kg), failed to influence either the occurrence of contrast or the attenuation of contrast by cyproheptadine. The results of Experiment 4 indicated that the contrast-reducing action of cyproheptadine was not mediated by the antihistaminergic properties of the drug since the antihistamine, pyrilamine (6 or 12 mg/kg), also failed to prevent the occurrence of contrast. Finally, the contrast-reducing action of cyproheptadine was not due to rate-dependent and/or appetite stimulating effects since cyproheptadine did not serve to increase lick frequency in rate-dependent controls.