Prolonged but not acute fluoxetine administration produces its inhibitory effect on hippocampal seizures in rats.
This study assessed the effects of acute as well as long-term administration of fluoxetine, a selective serotonin (5-HT) reuptake inhibitor with anti-depressant properties, on hippocampal (HIP) seizures elicited by electrical stimulation in rats. The fluoxetine effect on HIP seizures was also assessed following long-term treatment with gepirone, a 5-HT1A receptor agonist. Acute single administration of fluoxetine (1, 10 mg/kg; IP) was found to produce no significant effect on HIP seizure activity. Following daily IP administration of fluoxetine (10 mg/kg per day) or gepirone (10 mg/kg per day) for 21 days, animals were given a 7-day drug-free period and then challenged with an acute dose of 10 mg/kg fluoxetine. These treatment regimens resulted in a significantly increased afterdischarge threshold of HIP seizures in response to acute fluoxetine administration. The inhibitory effect of fluoxetine, however, was not present 4 weeks after long-term treatment with either fluoxetine or gepirone. The present results indicate that long-term treatment with these compounds enhances the antiepileptic effect of subsequent fluoxetine administration on the generation of HIP seizures. This effect is possibly related to the well-demonstrated evidence that fluoxetine and gepirone, on long-term treatment, facilitate net 5-HT neurotransmission through desensitization of presynaptic 5-HT autoreceptors.
Wada
Y
Y
Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.
Shiraishi
J
J
Nakamura
M
M
Hasegawa
H
H
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004558:Electric Stimulation; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000517:prevention & control; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology
D000927:Anticonvulsants; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D012965:Sodium Chloride; C039979:gepirone