The systemic or local administration of diverse antidepressants increases the neuronal firing rate of the lateral septal nucleus (LSN), whereas some stressful situations decrease its firing rate; however, any long-lasting effect exerted by the forced swimming (FS) test (15-min pretest and 5-min test 24 h later) on the firing rate of the LSN is unknown. Therefore, single-unit extracellular recordings were obtained from the LSN neurons of control rats (Ctrl, n=6) and FS rats (n=10) 2 h after the last swimming session. In other rats, spontaneous firing rate of cortical neurons was recorded under the same experimental conditions. The firing rate of the LSN neurons of the animals in the FS group was significantly lower (9.2+/-1.7 spikes/10 s; P<.004, n=35) in comparison with the Ctrl group (21.1+/-3.4 spikes/10 s, n=22). The reduced firing rate in the LSN after swimming tests was both evident and generalized given that approximately 83% of the total recorded neurons from the FS group fired below the mean+/-1 S.D. rate obtained from the Ctrl group. Accordingly, the mean first-order interval of neuronal firing rate in the FS group (621.3+/-22.6 ms) was significantly greater (P<.05) than that observed in the Ctrl group (391.5+/-29.2 ms), but no significant differences were found in the variation coefficient of these two experimental groups, illustrating regularity of firing. Nonsignificant differences or even an opposite trend were observed in the firing rate of cortical neurons in the FS group (26.3+/-8.4 spikes/10 s) as compared with Ctrl group (15.4+/-1.1 spikes/10 s). Accordingly, no differences were found in the variation coefficient (FS 55.3+/-7.2%, Ctrl 55.8+/-3.6%) or average first-order interval (FS 417.8+/-71.8 ms, Ctrl 494.1+/-64.5 ms). We conclude that the FS test constitutes a situation whose capacity for inducing long-lasting despair is reflected in a reduction in the firing rate of LSN neurons as it occurs in situations of anxiety and fear, contrary to the actions of antidepressant drugs.