Chronic but not acute Li+ treatment prevents behavioral depression in rats.

The effect of lithium administration on the learned helplessness model of depression was investigated. Female Wistar rats (190-210 g) received either tap water alone (N = 156) or 20 mM LiCL provided chronically (30 days; N = 127) or acutely (5 days; N = 22) in the drinking water. Three days before the end of treatment, each group was divided into two subgroups which received either inescapable shock (IS) or no shock (NS) treatment in shuttle boxes. All groups were subsequently submitted to an escape test on the following day and then sacrificed one day after the escape test, when blood samples were taken to measure serum Li+, Na+ and K+ concentrations by flame photometry. There were no significant differences in serum Na+ amongst the 4 groups. Chronically treated NS and IS rats both presented an increase in serum K+ compared to the control rats. The IS and not the NS chronically treated rats presented increased serum Li+ levels which cannot be accounted for in terms of differences in Li+ intake. The IS group treated chronically with lithium had a better escape performance than the IS group receiving either tap water or acute Li+ administration. We conclude that chronic but not acute Li+ treatment at a serum level within the prophylactic range (0.5 mEq/l) is able to prevent learned helplessness in the rat. These results agree with the data obtained in clinical practice indicating that Li+ is only effective after chronic administration and that Li(+)-induced hyperkalemia is a side effect.