Artigo de Periódico
Hyperglycemia induced by acute central fluoxetine administration: role of the central CRH system and 5-HT3 receptors
Fecha
2004Registro en:
0143-4179
v. 38, n. 2-3
Autor
Carvalho, F.
Barros, D.
Silva, J.
Rezende, E.
Soares, M.
Fregoneze, J.
Silva, E. De Castro e
Carvalho, F.
Barros, D.
Silva, J.
Rezende, E.
Soares, M.
Fregoneze, J.
Silva, E. De Castro e
Institución
Resumen
Brain serotonin and CRH systems participate in the control of blood glucose levels. We have previously demonstrated that the
pharmacological stimulation of central 5-HT3 receptors, the target for several therapeutic agents used as antiemetics in the course of
chemotherapy, induces hyperglycemia. The aim of the present study was to investigate the participation of the brain CRH component
and 5-HT3 receptors in basal blood glucose levels as well as in the hyperglycemia induced by third ventricle injections of
fluoxetine, a serotonin reuptake inhibitor with a broad range of clinical use. In this study, we used fasted adult Wistar male rats
(220 20 g) whose third ventricles were cannulated 7 days prior to the experiments. Acute third ventricle injections of fluoxetine
caused a significant increase in plasma glucose levels throughout the experiment. Pretreatment with a-helical CRH, a selective CRH
antagonist, significantly blunted fluoxetine-induced hyperglycemia. Also, pretreatment with two distinct selective 5-HT3 receptor
antagonists (LY-278,584 and ondansetron) significantly impaired the rise in plasma glucose levels observed in fluoxetine-treated
animals pretreated with isotonic saline solution. None of these antagonists was able to modify blood glucose levels when injected
alone into the third ventricle. Animals receiving third ventricle injections of fluoxetine, in spite of being hyperglycemic, presented
plasma insulin levels similar to those displayed by normoglycemic, saline-treated controls. It is suggested that the acute increase in
brain serotonergic activity caused by third ventricle injections of fluoxetine induces a hyperglycemic response that requires the
functional integrity of the brain CRH system and 5-HT3 receptors. Also, it is proposed that the absence of a compensatory increase
in plasma insulin levels may contribute to the generation of a hyperglycemic response after central fluoxetine administration