- Abstract 1. 1. Hypokinesia following immobilization stress in rats is attenuated by anti-depressant drugs used in the treatment of unipolar depression. Lithium has anti-depressant effects both clinically and in other animal models of depression, but the mechanism of its antidepressant effect has not been elucidated. 2. 2. To determine if lithium reverses immobilization-induced hypokinesia, the effects of lithum and immobilization stress were tested in a fully factorial 2 × 2 design. 3. 3. Half the rats were fed chronic dietary lithium, while the other half ate regular chow. Half of each group were exposed to one hour immobilization, while the other half remained in their home cages until the test. Activity was measured for 20 min in an automated activity meter. 4. 4. Stress significantly reduced activity, but a significant interaction between stress and lithium was found, indicating that lithium attenuated the effect of stress. 5. 5. Lithium-induced attenuation of immobilization stress may serve as an animal model for the anti-depressant effects of lithium.