Pindolol potentiates the effect of fluoxetine on hippocampal seizures in rats

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• 作者：Wada ; Yuji ; Hirao ; Naohisa ; Shiraishi ; Jun ; Nakamura ; Mitsuhiko ; Koshino ; Yoshifumi
• 关键词：Epilepsy ; Serotonin ; Fluoxetine ; Pindolol ; 5-HT_1A receptors ; Seizure ; Hippocampus
• 刊名：Neuroscience Letters
• 出版年：1999
• 出版时间：May 21, 1999
• 年：1999
• 卷：267
• 期：1
• 页码：61-64
• 全文大小：120 K

文摘

Recent studies have shown that behavioral and neurochemical changes induced by selective serotonin (5-HT) reuptake inhibitors such as fluoxetine are potentiated by coadministration of a 5-HT_1A receptor antagonist. The present study assessed the effects of concomitant administration of fluoxetine and a 5-HT_1A receptor antagonist, pindolol, on focal hippocampal (HIP) seizures elicited by electrical stimulation in rats. A 10 mg/kg dose of fluoxetine, which was ineffective by itself, produced a significant increase in the afterdischarge threshold of HIP seizures when combined with pindolol at 10 mg/kg. The inhibitory effect of this combination was eliminated by pretreatment with parachlorophenylalanine, a depletor of brain 5-HT. These findings suggest that treatments designed to increase 5-HT neurotransmission inhibit the generation of HIP seizures. A combination of fluoxetine with a 5-HT_1A receptor antagonist could thus be therapeutically useful for the treatment of depressive symptoms in patients with epilepsy.