Serotonin reuptake blocker fluoxetine suppresses hippocampal theta oscillation in rabbits during EEG

In earlier studies it has been shown that stimulation of the median raphe nucleus (MR) in awake rabbits decreases the expression and frequency of oscillatory theta activity in the septohippocampal system, and the functional blockade of this nucleus evokes the regular and high-frequency theta rhythm. The present work was aimed at elucidation of serotoninergic influence of MR (which also contains cells of other chemical nature) to the septohippocampal system of theta activity. Serotonin reuptake blocker fluoxetine that increases brain serotonin level was applied. Hippocampal electroencephalogram was recorded in awake rabbits. Bilateral intracerebroventricular infusion of fluoxetine hydrochloride (Sigma, St. Louis; 15 micrograms in 5 microliters saline) in all cases reduced the rhythmic theta activity. In 15 of 18 (83.3%) of experiments the decrease in hippocampal theta oscillations was more than 50% of the control level. The theta band of the spectral density histogram decreased in the mean by 56 +/- 5.8% of the control level (from 10 to 93% in different experiments, p < 0.001). The mean latency of these changes was 3.5 +/- 0.11 minutes (2.9-4.1 min), the effect duration was 64 +/- 3.2 min (45.3-90 min). The mean frequency of the theta waves did not change as compared to the baseline and was equal to 5.25 +/- 0.5 Hz (4.5-6.5 Hz). The fluoxetine-induced reduction of the theta rhythm expression in hippocampus is the evidence of its inhibitory control by serotoninergic brain system. It is suggested that the increase of the frequency of hippocampal theta rhythm after the functional blockade of MR observed in our earlier experiments was the result of a release of the septohippocampal system from the influence of nonserotoninergic neurons (via glutamatergic reticular formation) and/or temporary cessation of the MR interaction with noradrenergic, dopaminergic and glutamate/aspartate systems.