CHRONIC BUT NOT ACUTE LI+ TREATMENT PREVENTS BEHAVIORAL DEPRESSION INRATS

The effect of lithium administration on the learned helplessness model of depression was investigated. Female Wistar rats (190-210 g) receiv ed 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 t wo subgroups which received either inescapable shock (IS) or no shock (NS) treatment in shuttle boxes. All groups were subsequently submitte d to an escape test on the following day and then sacrificed one day a fter the escape test, when blood samples were taken to measure serum L i+, Na+ and K+ concentrations by flame photometry. There were no signi ficant differences in serum Na+ amongst the 4 groups. Chronically trea ted 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 prese nted increased serum Li+ levels which cannot be accounted for in terms of differences in Li+ intake. The IS group treated chronically with l ithium had a better escape performance than the IS group receiving eit her tap water or acute Li+ administration. We conclude that chronic bu t not acute Li+ treatment at a serum level within the prophylactic ran ge (0.5 mEq/l) is able to prevent learned helplessness in the rat. The se results agree with the data obtained in clinical practice indicatin g that Li+ is only effective after chronic administration and that Li-induced hyperkalemia is a side effect.