A comparison of the behavioural effects of 5-HT2A and 5-HT2C receptor agonists in the pigeon

Activity at the 5-HT2A receptor versus that of the 5-HT2C receptor was stud ied in three behavioural paradigms. In pigeons trained to discriminate 0.32 mg/kg of 1-(2,5-diemethoxy-4-iodophenyl)-2-aminopropane (DOI) (a mixed 5-H -2A/C receptor agonist) from vehicle, quipazine (0.1-1 mg/kg) and m-chlorop henylpiperazine (mCPP) (1-3 mg/kg) substituted for DOI in a dose-related ma nner, and this generalization was blocked by MDL100907 (0.0001-0.01 mg/kg), a selective 5-HT2A receptor antagonist. RO60-0175 (a relatively selective 5-HT2C agonist) induced partial substitution at 3 mg/kg that was antagonize d by both MDL100907 and by 3 mg/kg of SB242084, a relatively selective 5-HT 2C antagonist. MK212 (a mixed 5-HT2C/A agonist) induced partial substitutio n that was antagonized by SB242084, but not by MDL100907. On a progressive ratio 5 operant schedule (PR5) for food reinforcement, DOI, quipazine, mCPP , MK212 and RO60-0175 decreased the break point; mCPP, DOI, MK212 and quipa zine also induced vomiting. Although MDL100907 antagonized both the reducti ons of break point and vomiting, SB242084 only partially attenuated the dec rease in break point observed with MK212 and DOI, and was unable to elimina te vomiting. Thus pharmacological activity at the 5-HT2A receptor can be be haviourally distinguished from pharmacological activity at the 5-HT2C recep tor in the pigeon. Furthermore, the decrease in the break point of a PR5 sc hedule induced by 5-HT2C receptor agonists may be related to decreased appe tite, whereas that induced by 5-HT2A receptor agonists may be due to unrela ted factors, such as emesis. (C) 2000 Lippincott Williams & Wilkins.