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 susp ension 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 ambu lation in an open-field. I.c.v. injection of GMP (320-480 nmol/site) also r educed the immobility in the FST without affecting ambulation. The immobili ty of mice treated with MK-801 (0.01 mg/kg) + GMP (50 mg/kg) was not signif icantly different from the result obtained with MK-801 or GMP alone, but GM P (or MK-801) + imipramine (15 mg/kg) treatment induced a stronger effect i n FST than administration of either drug alone. Pretreatment with p-chlorop henylalanine (100 mg/kg, 4 days) completely blocked the anti-immobility eff ect of GMP, MK-801 or fluoxetine (32 mg/kg), but only partially that of imi pramine in the FST. The results suggest that the antidepressant-like effect s produced by the administration of GMP, like MK-801, may be due to an indi rect serotonin activation resulting from blockade of NMDA receptors. NeuroR eport 11:[839-1843 (C) 2000 Lippincott Williams & Wilkins.