ADDITIVE EFFECTS OF LITHIUM AND ANTIDEPRESSANTS IN THE FORCED SWIMMING TEST - FURTHER EVIDENCE FOR INVOLVEMENT OF THE SEROTONINERGIC SYSTEM

In the mouse forced swimming test (FST) pretreatment with a subactive dose of lithium (1 mEq/kg), given IP 45 min before the test, facilitat ed the antidepressant activity of iprindole, fluoxetine, and moclobemi de (given IP 30 min before the test). These antidepressants (ADS) were not active alone in the FST in this study. Moreover, when subactive l ithium was combined with a wide range of ADS, each given at subactive doses, those ADS with serotoninergic properties (e.g. imipramine, cita lopram, paroxetine, fluoxetine, trazodone, mianserin, and moclobemide) significantly reduced immobility times. ADS acting primarily on norad renaline (NA) or dopamine (DA) systems (desipramine, maprotiline, vilo xazine, and bupropion) did not significantly decrease immobility when given in combination with lithium. This was also the case for RO 16 64 91 [a reversible, B specific monoamine oxidase inhibitor (MAOI)], nial amide, and pargyline (both irreversible, mixed MAOIs), The anti-immobi lity effect of iprindole in combination with lithium suggests either a direct or indirect action on the serotonin (5HT) system by this ADS w hose mechanism of action remains obscure. These results, using an anim al behavioral model of depression and combining our present knowledge of the acute action of various ADS, support the hypothesis that the po tentiation by lithium of ADS is via direct 5HT mechanisms,indirectly v ia a NA/5HT link, and/or by second messenger systems. Lithium may also facilitate the expression of antidepressant activity of ADS not activ e by themselves in the FST.