[Serotonergic mechanisms of hippocampal kindled seizures in cats--effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and ketanserin].
Based on our previous findings that a serotonin (5-HT) precursor L-5-hydroxytryptophan and a 5-HT1 a receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin can suppress seizures kindled from the feline hippocampus (HIP), we have suggested that 5-HT1 a receptors play an inhibitory role in HIP seizure generation. In order to clarify the role of 5-HT2 receptors in epilepsy, the present study examined the effects of a 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane(DOI) and a 5-HT2 receptor antagonist ketanserin on HIP-kindled seizures. Following the completion of HIP kindling, five cats received intravenous injections of 0.9% saline, DOI (1.0mg/kg) or ketanserin (1.0mg/kg). Electrical stimulation at the generalized seizure triggering threshold was delivered to the kindled HIP 15 min after drug administration. The anticonvulsant effects were assessed by the behavioral seizure stage, afterdischarge duration, latency to the onset of stages 4 and 6, and duration of a generalized tonic-clonic convulsion (GTC). Although no significant change was found in the seizure stage following the administration of either drug, both DOI and ketanserin significantly altered the latency for seizure generalization. DOI significantly reduced the latency to the onset of stage 6 GTC as compared with saline, with a significant reduction in the afterdischarge duration. In contrast, ketanserin significantly increased the latency to the GTC onset as compared with saline. Neither the latency of the stage 4 onset nor the GTC duration was significantly affected by these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakamura
M
M
Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.
Wada
Y
Y
Hasegawa
H
H
Yamaguchi
N
N
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004827:Epilepsy / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology*; D007696:Kindling, Neurologic; D011985:Receptors, Serotonin / Q000502:physiology; D012640:Seizures / Q000517:prevention & control; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine