Depression is one of the most common affective disorders. According to the World Health Organization (WHO), it is currently the fourth major global health problem (Kessler et al. 2003). The growing number of people suffering from depression has motivated the scientists to search for new antidepressant drugs. Since numerous studies revealed that NMDA receptor may be involved in the mechanism of action of the antidepressant agents, modulation of the NMDA receptor function by different ligands has been taken into consideration. There are some promising results demonstrating the antidepressant activity of the antagonists binding to the polyamine site of the NMDA receptor complex. Ifenprodil belongs to a family of the selective, atypical non-competitive antagonists of the NMDA receptors. It acts via inhibition of the polyamine binding site of the NR2B subunit (Williams 1993). An antidepressantlike effect of ifenprodil was observed in several behavioral studies, for example in the forced swimming test (Carter et al. 1990, Williams 1993, Layer et al. 1995, Scolnik 1999, Paoletti and Neyton 2007). It was shown that its antidepressant-like activity is increased by other antidepressant drugs (imipramine and fluoxetine). The aim of our work was to evaluate the antidepressant activity of the joint administration of ifenprodil and NMDA ligands in the mouse forced swimming test (FST). The experiments were carried out on male Albino Swiss mice. In order to avoid the risk of obtaining the false positive/negative effects in the FST test caused by a possible influence of the tested substances on the locomotor activity, the spontaneous locomotor activity was measured. The obtained results demonstrated that ifenprodil at the dose of 10 mg/ kg enhances the antidepressant-like effect of the following NMDA receptor ligands: a competitive NMDA receptor antagonist – CGP 37849 (0.312 mg/kg), an antagonist at glycine site – L-701,324 (1 mg/kg) and a non-competitive antagonist at phencyclidyne – MK801 (0.05 mg/kg). However, it did not potentiate the antidepressant activity of the inorganic modulators of the NMDA receptor complex, such as Zn2+ (2.5 mg/kg) and Mg2+ (10 mg/kg). Treatment with the tested agents did not influence the locomotor activity. In conclusion, our findings indicated that antidepressant-like activity of ifenprodil is connected with serotoninergic and glutamatergic system.
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