5-HT2 modulation of AY-9944 induced atypical absence seizures.
We investigated the role of 5-HT(2A) and 5-HT(2C) receptors in atypical absence seizures (AAS) induced by trans-1,4-bis[2-chloro-benzylaminomethyl] cyclohexane, dihydrocholoride (AY-9944). The total duration and number and mean duration of the spontaneous bursts of slow spike-and-wave discharges (SSWD) that characterize the AY model were measured using electrocorticographic (ECoG) recordings in freely moving animals. In a randomized counterbalanced dose response design, rats were treated with either the 5-HT(2A) agonist 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI, 0.5, 1 or 2 mg/kg), the 5-HT(2C) preferring agonist m-chlorophenylpiperazine (mCPP, 1, 2, or 4 mg/kg), the 5-HT(2A) antagonist ketanserin (2.5 or 5 mg/kg), or vehicle. DOI significantly reduced the total duration and number of SSWD. In contrast, mCPP had no effect on total duration or number of SSWD. Ketanserin exacerbated the number of SSWD at 2.5 mg/kg but produced mixed results at 5.0 mg/kg. However, none of the treatments affected the mean SSWD duration. These data support the hypothesis that 5HT(2A) receptors are involved in the pathology of experimental atypical absence seizures.
Bercovici
Eduard
E
Institute of Medical Science, University of Toronto, Toronto, Canada.
Cortez
Miguel A
MA
Snead
O Carter
OC
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000633:toxicity*; D004832:Epilepsy, Absence / Q000139:chemically induced* / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride / Q000633:toxicity*
D000662:Amphetamines; D000924:Anticholesteremic Agents; D010879:Piperazines; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine