Neuropharmacology Poster Session
Paz-Valiñas, L. (Dept. Fisiología Animal; Fac. de Biología; Universidad de Santiago de Compostela, Spain)
Aldegunde, M. (Dept. Fisiología Animal; Fac. de Biología; Universidad de Santiago de Compostela, Spain)
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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|Míguez, J.M.; Paz-Valiñas, L.; Aldegunde, M.; (1998). The Ability of (-)-Pindolol to Block the Paroxetine-Induced Decrease in the Release of Serotonin in the Ventral Hippocampus of the Rat.. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/neuropharm/miguez0725/index.html|
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