Prolonged but not acute fluoxetine administration produces its inhibitory effect on hippocampal seizures in rats

Psychopharmacology (Berl). 1995 Apr;118(3):305-9. doi: 10.1007/BF02245959.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Electric Stimulation
  • Fluoxetine / pharmacology*
  • Hippocampus / drug effects*
  • Injections, Intraperitoneal
  • Male
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Wistar
  • Seizures / prevention & control
  • Serotonin Receptor Agonists / pharmacology
  • Sodium Chloride / pharmacology


  • Anticonvulsants
  • Pyrimidines
  • Serotonin Receptor Agonists
  • Fluoxetine
  • Sodium Chloride
  • gepirone