1. The effect of chronic lithium (Li) administration in a learned helplessness (LH) model was investigated. Female Wistar rats (190-210 g) received either tap water ad libitum (N = 56) or 20 mM LiCl (N = 63) in the drinking water or were water restricted (35% based on lower liquid intake of rats receiving lithium, N = 40) for 30 days. On the 28th day, each of these groups was divided into three subgroups which received escapable (ES), inescapable (IS) or no shock (NS) treatment in shuttle boxes. All groups were submitted to the escape test on the 29th day and sacrificed on the 30th day, when blood samples were taken for measurement of serum lithium, sodium and potassium concentrations. 2. The NS group had lower serum Li levels (0.36 +/- 0.06, N = 15) than the ES (0.46 +/- 0.07, N = 15) or IS group (0.44 +/- 0.09, N = 25). The Li-pretreated group subjected to IS had a more effective escape performance than the IS group under water restriction and showed the same behaviour as animals not submitted to shocks. 3. We conclude that chronic treatment with Li at a serum level of 0.44 +/- 0.09 mEq/l prevents learned helplessness in rats. These results corroborate the validity of the use of this model for the assessment of the capacity of Li to protect against some depressive episodes.261201-12