Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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It has been suggested that the selective serotonin reuptake inhibitors (SSRIs) exert their antidepressant activity by increasing the concentration of serotonin (5-HT) in the extracellular compartment, thereby enhancing serotonergic neurotransmission. However, recent evidence showed that the acute administration of SSRIs inhibits 5-HT release activity through an increase in the extracellular 5-HT levels in the dorsal and median raphe nuclei and, in turn, the stimulation of 5-HT1A autoreceptors. The blockade of these receptors by selective 5-HT1A receptor antagonists has been shown to facilitate the effect of SSRIs on extracellular 5-HT in various terminal regions of the rat brain. The present study investigates the ability of (-)-pindolol, a 5-HT1A antagonist, to block the paroxetine-induced decrease in 5-HT release activity in the ventral hippocampus of the anesthesized rat by using a microdialysis technique. In all experiments, 3 micromolar paroxetine was continuosly perfused through the dialysis probe located in the hippocampus. In this experimental condition, the systemic administration of paroxetine (10 mg/kg, i.p.) induced a 66% decrease in the extracellular 5-HT levels of the hippocampus. The combination of paroxetine and pindolol (5 mg/kg, s.c.) blocked the paroxetine-induced decrease in hippocampal 5-HT. Moreover, the local perfusion with (-)-pindolol (10 and 100 micromolar for 30 min) in the median raphe induced a dose-dependent recovery of the paroxetine-induced decrease in the extracellular 5-HT levels of the hippocampus. These data suggest that (-)-pindolol may enhance the action of the SSRI paroxetine by mean of its antagonist properties on the 5-HT1A receptors located in the somatodendritic areas.

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Poster Number PAmíguez0725
Keywords: Paroxetine, Microdialysis, (-)-Pindolol, Hippocampus, Serotonin release