Acute treatments with GMP produce antidepressant-like effects in mice

This study examined the effect of GMP in two models of depression in mice. The immobility times in the forced swimming test (FST) and in the tail suspension test (TST) were significantly reduced by GMP (dose range: 5-50 mg/kg and 5-100 mg/kg, i.p., respectively), without accompanying changes in ambulation in an open-field. I.c.v. injection of GMP (320-480 nmol/site) also reduced the immobility in the FST without affecting ambulation. The immobility of mice treated with MK-801 (0.01 mg/kg) + GMP (50 mg/kg) was not significantly different from the result obtained with MK-801 or GMP alone, but GMP (or MK-801) + imipramine (15 mg/kg) treatment induced a stronger effect in FST than administration of either drug alone. Pretreatment with p-chlorophenylalanine (100 mg/kg, 4 days) completely blocked the anti-immobility effect of GMP, MK-801 or fluoxetine (32 mg/kg), but only partially that of imipramine in the FST. The results suggest that the antidepressant-like effects produced by the administration of GMP, like MK-801, may be due to an indirect serotonin activation resulting from blockade of NMDA receptors.