Studies on the role of serotonin in different regions of the rat central nervous system on pentylenetetrazol-induced seizures and the effect of di-n-propylacetate.
5,7-Dihydroxytryptamine (5,7-DHT) injections which caused selective depletion of serotonin in the forebrain enhanced the seizures caused by pentylenetetrazol (PTZ 90 mg/kg s.c.) in rats. No effect was observed in rats with 5,7-DHT-induced depletion of spinal serotonin or treated with metergoline (1 mg/kg i.p.) or methysergide (10 mg/kg i.p.). The various procedures aimed at decreasing serotonin transmission did not significantly modify the effect of di-n-propylacetate (DPA) on tonic seizures and mortality caused by PTZ but significantly reduced the DPA-induced increase in the latency to the first convulsion. More animals with clonic seizures were seen in the DPA-treated group which had been subjected to selective depletion of spinal serotonin or treated with methysergide than in DPA-treated controls. Combined treatment with d-fenfluramine (1.25 mg/kg i.p.) and DPA (75 mg/kg i.p.), doses which by themselves had no significant effect, reduced tonic seizures and mortality caused by PTZ. The results show that a diffuse deficit in forebrain serotonin enhances PTZ-induced seizures. Serotonin does not play an important role in the effect of DPA against PTZ-DPA on clonic convulsions. Agents increasing serotonin transmission may enhance the anticonvulsant activity of DPA.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000502:physiology*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D012640:Seizures / Q000139:chemically induced*; D012701:Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D008711:Metergoline; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D014635:Valproic Acid; D010433:Pentylenetetrazole; D008784:Methysergide