The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of lateral septal nucleus neurones in the rat

The administration of a relatively high dose of antidepressant drugs produces an increased neuronal firing rate of the lateral septal nucleus (LSN) in the rat and a decreased immobility in rats forced to swim. However, it is unknown whether a minimally effective low-dose 21-day treatment with the selective serotonin reuptake inhibitor, fluoxetine, while reducing immobility in the forced swim test, also increases the neuronal firing rate of the LSN in Wistar rats. The total time of immobility decreased with a daily injection of 0.5. 1.0 or 2.0 mg/kg of fluoxetine (p < 0.001), and the lowest dose increasing the latency to the first immobility period (p < 0.0001) was 1.0 mg/kg. Therefore, the action of the 21-day fluoxetine treatment (1.0 mg/kg) on the firing rate of LSN neurones was tested in another group of rats. A total amount of 78 single-unit extracellular recordings was taken from the LSN of eight control rats (n = 40) and eight fluoxetine treated rats (n = 38). The LSN firing rate in the fluoxetine group was double (18.3 +/- 2.5 spikes per 10 s, p < 0.05) that in the control group (7.0 +/- 0.9 spikes per 10 s), and the first order interval of firing proved to be significantly lower in the fluoxetine group compared to the control group (384.3 +/- 22.3 and 639.7 +/- 27.5 ms, respectively; p < 0.05). In conclusion, the increased neuronal firing rate of the LSN in the animals treated with a low dose of fluoxetine may be associated with an increased motivation to escape from the stressful situation that the forced swim represents.