Considerable attention has been paid to a possible role of immunological dysregulation in the pathogenesis of depression. It has been reported that combined administration of antidepressant drugs and the non-competitive NMDA receptor antagonist amantadine (AMA) reduces immobility time in the forced swimming test. Moreover, preliminary clinical data show that such a combination of drugs has benefi cial effects in treatment-resistant depressed patients. Since immune activation and a pro-infl ammatory response are clearly evident in treatment-resistant depression, the aim of the present study was to examine the effect of an antidepressant combination of FLU and AMA on immune parameters in rats subjected to the forced swimming test. The obtained results revealed synergistic antidepressant effects of combined administration of FLU (10 mg/kg) and AMA (10 mg/kg) – drugs otherwise ineffective when given separately in such doses. The antidepressant activity was accompanied with a reversal of the stress-induced increase in the proliferation of splenocytes in response to concanavalin A, and a signifi cant enhancement in the production of the negative immunoregulator interleukine-10. Moreover, the relative spleen weight in these rats was also reduced after joint administration of FLU with AMA in comparison with rats treated with the vehicle. In summary, the antidepressive effi cacy of a combination of FLU and AMA given in suboptimal doses may be related to their negative immune effects.
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