Antidepressant-like Effects of Neferine in the Forced Swimming Test Involve the Serotonin1A (5-HT1A) Receptor in Mice

The effects of neferine, an alkaloid of Nelumbo nucifera Gaertner embryos, on immobility in the forced swimming test, which is used to evaluate antidepressants, were investigated in mice. The administration of neferine from 25 to 100 mg/kg i.p. elicited anti-immobility effects in mice. The molecular dose effects of neferine in the forced swimming test were almost equal to those of the typical antidepressants maprotiline and imipramine. The involvement of the 5-HT receptor subtypes was also studied using 5-HT receptor antagonists. Anti-immobility effects of neferine are antagonized by the serotonin1A (5-HT1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT1B receptor antagonist, 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl] benzamide dihydrochloride (GR 55562), the 5-HT2 receptor antagonist, 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT3 receptor antagonist, ondansetron and the 5-HT4 receptor antagonist, 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not affect the anti-immobility effects of neferine. The anti-immobility effect of the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetaralin (8-OH-DPAT) was also antagonized by WAY 100635. Furthermore, co-administration of subactive doses of neferine (10 mg/kg) and 8-OH-DPAT (0.1 mg/kg) produced synergistic antidepressant-like effects. These results suggest that neferine shows antidepressant-like effects in mice similar to typical antidepressants and that these effects are mediated by the 5-HT1A receptor. Therefore, the central effects of neferine are likely to be linked to serotonergic neurotransmission.