EN
Depression is one of the most frequent chronic and life-debilitating health problems in the world. Though its epidemiology, risk factors and development have been continuously studied for decades, the optimal treatment of the depressed patients still remains an important clinical dilemma. The conventional antidepressant therapy is not sufficient due to the common ineffectiveness and adverse reactions. The search for better alternatives seems to be crucial. Recently, much consideration has been given to both totally novel chemical compounds as well as to the unique combinations of the well-known drugs. The use of the NMDA receptor ligands, particularly in co-administration with other agents exerting the antidepressant activity, emerged amongst the new ideas. The main objective of our study was to evaluate the influence of caffeine on the antidepressant-like activity of various NMDA receptor modulators. The antidepressant-like effect was assessed by the forced swim test in mice. The obtained results demonstrated the significant interaction between caffeine (5 mg/kg) and the following NMDA receptor ligands: CGP 37849 (0.312 mg/kg), L-701,324 (1 mg/kg) and D-cycloserine (2.5 mg/ kg). Interaction between caffeine and the inorganic modulators, i.e. Zn2+ (2.5 mg/kg) and Mg2+ (10 mg/kg), was not considered as significant. The antidepressant-like potential of the NMDA receptor ligands (except for Zn2+ and Mg2+) given concomitantly with caffeine was reinforced. The possible mechanism of the observed interaction may involve the influence of caffeine on the glutamatergic system.