Effect of amantadine and imipramine on immunological parameters of rats subjected to a forced swimming test

The activation of cell-mediated immunity and the hypothalamic-pituitary-adrenal axis may play a role in the pathophysiology of depression, especially a treatment-resistant one, and antidepressant treatments may exert their effect by suppressing this activation. In our previous studies we described synergistic, antidepressant-like effects of a combination of amantadine (10 mg/kg) and imipramine (5 mg/kg) - drugs otherwise ineffective when given separately in such doses - in the forced swimming test (FST), an animal model of depression. Moreover, preliminary clinical data show that the above-described combination has beneficial effects on treatment-resistant patients. However, it is still unknown whether these positive effects of combined treatment with amantadine and imipramine on behavioural depressive changes are accompanied with normalization of immunoendocrine parameters. Therefore, the present study was aimed at ascertaining whether the antidepressive effect of a combination of amantadine and imipramine was accompanied with a decrease in some immunoendocrine parameters. The antidepressant activity was accompanied with a reversal of the stress-induced increase in the proliferation of splenocytes in response to concanavalin A (ConA). Imipramine, amantadine and a combination of amantadine and imipramine enhanced the production of the negative immunoregulator IL-10 in rats subjected to the FST. The exposure to the FST produced an increase in plasma corticosterone levels, which was significantly attenuated by pretreatment with imipramine or amantadine (a combination of imipramine and amantadine causes reduction within the margin of error). In summary, the antidepressive efficacy of a combination of amantadine and imipramine given in suboptimal doses may be related to their negative immunoendocrine effects.