Introduction: Celastrus paniculatus seed oil, commonly known as Malkangni or Jyotishmati, was in use from time immemorial to treat brain related disorders. Celastrus paniculatus seed oil has significant antidepressant-like activity in chronic unpredictable stressed mice. The present study was undertaken to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil in unstressed mice and to explore its mechanism of action.
Methods: The seed oil (50, 100, and 200 mg/kg, PO) and fluoxetine per se were administered for 14 successive days to Swiss young albino mice. On the 14th day, 60 min after drug administration, animals were subjected to Tail Suspension Test (TST) and Forced Swim Test (FST). The mechanism of action was also studied.
Results: The oil significantly decreased immobility period of mice in both tail suspension test and forced swim test, indicating its significant antidepressant-like activity. The efficacy was found to be comparable to fluoxetine (P<0.0001). ED50 value of celastrus seed oil using FST and TST were 17.38 and 31.62 mg/kg, respectively. The oil did not show any significant effect on locomotor activity. It significantly inhibited brain MAO‒A activity and decreased plasma corticosterone levels. Sulpiride
(selective D2-receptor antagonist), p-CPA (tryptophan hydroxylase inhibitor), and baclofen (GABAB agonist) significantly attenuated the oil-induced antidepressant-like effect, when assessed during TST. 

Discussion: Celastrus paniculatus seed oil produced significant antidepressant-like effect in mice possibly through interaction with dopamine D2, serotonergic, and GABAB receptors as well as inhibition of MAO‒A activity and decrease in plasma corticosterone levels.