Monoaminergic and aminoacidergic receptors are involved in the antidepressant-like effect of ginsenoside Rb1 in mouse hippocampus (CA3) and prefrontal cortex.

Ginsenoside Rb1 (Rb1), as the major bioactive ingredient of Panax ginseng C.A. Meyer, elicited a novel antidepressant-like effect in the forced swim test (FST) in chronic unpredictable mild stress (CUMS) rats in our previous study. To further explore the molecular mechanism of Rb1 on the neurotransmitters such as 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), norepinephrine (NE), dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), glutamate (Glu) and gamma-aminobutyric acid (GABA) in this antidepressant-like effect, the neurochemical changes in the monoaminergic and aminoacidergic receptors were investigated in the present pharmacological study by using reuptake inhibitors, receptors agonists and antagonists. The results showed that a sub-effective dose of Rb1 (5 mg/kg, p.o.) co-administered with fluoxetine (1 mg/kg, i.p., a selective serotonin reuptake inhibitor), reboxetine (2.5 mg/kg, i.p., a noradrenalin reuptake inhibitor), bupropion (10 mg/kg, i.p., a dopaminergic reuptake inhibitor), Mk-801 (0.05 mg/kg, i.p., an N-methyl-d-aspartic acid (NMDA) receptor antagonist) or baclofen (0.1 mg/kg, i.p., a selective GABA agonist) significantly decreased the immobility time in the FST. In addition, pretreating mice with NAN190 (0.5 mg/kg, i.p., a 5-HT1A receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT3A receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, i.p., a selective D1 receptor antagonist), haloperidol (0.2 mg/kg, i.p., a non-selective D2 receptor antagonist), NMDA (75 mg/kg, i.p., an agonist at the glutamate site) or bicuculline (4 mg/kg, i.p., a competitive GABA antagonist) reversed the antidepressant-like effect of Rb1 (10 mg/kg, p.o.) in the FST. The results obtained for the neurotransmitters in the mouse hippocampus (CA3) and prefrontal cortex showed that Rb1 up-regulated the levels of 5-HT, 5-HIAA, NE, DA, and GABA and decreased the level of Glu. However, there were no significant differences in HVA or DOPAC. Furthermore, there were no significant alterations in the total path of spontaneous locomotor activity in all treatments. These results suggest that both monoaminergic (serotonergic, noradrenergic and dopaminergic) and aminoacidergic (glutamatergic and GABAergic) receptors may be involved in the antidepressant-like effect of Rb1.