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

J Pharm Pharmacol. 1993 May;45(5):473-5. doi: 10.1111/j.2042-7158.1993.tb05578.x.


The anti-immobility effect of fluoxetine (40 mg kg-1) in the forced swimming test in mice was antagonized by the 5-HT1c/2 antagonist mesulergine (7.5 mg kg-1) and the dopamine D2 antagonist (+/-)-sulpiride (12.5 mg kg-1) but not by the 5-HT2/1C antagonist ritanserine (2 mg kg-1), the 5-HT1A/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 pretreatment 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-HT1C receptor.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Depression / drug therapy
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Ergolines / pharmacology*
  • Fluoxetine / antagonists & inhibitors*
  • Immobilization / physiology*
  • Male
  • Mice
  • Neurotransmitter Uptake Inhibitors / pharmacology
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Swimming


  • Ergolines
  • Neurotransmitter Uptake Inhibitors
  • Receptors, Serotonin
  • Fluoxetine
  • mesulergine