Pindolol potentiates the effect of fluoxetine on hippocampal seizures in rats.
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-HT1A receptor antagonist. The present study assessed the effects of concomitant administration of fluoxetine and a 5-HT1A 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-HT1A receptor antagonist could thus be therapeutically useful for the treatment of depressive symptoms in patients with epilepsy.
Wada
Y
Y
Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.
Hirao
N
N
Shiraishi
J
J
Nakamura
M
M
Koshino
Y
Y
D000818:Animals; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D010869:Pindolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D005473:Fluoxetine; D010869:Pindolol; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors