Mesulergine antagonism towards the fluoxetine anti-immobility effect in the forced swimming test in mice

Abstract— The anti-immobility effect of fluoxetine (40 mg kg^?1) in the forced swimming test in mice was antagonized by the 5-HT_1c/2 antagonist mesulergine (7·5 mg kg^?1) and the dopamine D₂ antagonist (±)-sulpiride (12.5 mg kg^?1) but not by the 5-HT_2/1C antagonist ritanserine (2 mg kg^?1), the 5-HT_1A/1B antagonist (–)-propranolol (20 mg kg^?1) or the 5-HT₃ antagonist DAU 6215 (0·1 mg kg^?1). All compounds were administered intraperitoneally (i.p.) 6 min before fluoxetine, given i.p. 30 min before testing. The anti-immobility effect of fluoxetine was also prevented by pretreat-ment with p-chlorophenylalanine (300 mg kg^?1 twice daily for 3 days) which produced an 80% reduction of 5-HT in brain. The results suggest that fluoxetine reduces immobility time in mice forced to swim, by acting indirectly through a mesulergine-sensitive site, probably the 5-HT_1C receptor.