Serotonergic modulation of absence-like seizures in groggy rats: A novel rat model of absence epilepsy

To explore the role of the serotonergic system in modulating absence seizures,we examined the effects of 5-ht1a and 5-ht2 agonists on the incidence of spike-and-wave discharges (swd) in groogy (gry) rats,a novel rat model of absence-like epilepsy. gry rats exhibited spontaneous absence-like seizures characterized by the incidence of sudden immobile posture and synchronously-associated swd. the total duration of swd in gry rats was about 300 - 400 s/15-min observation period under the control conditions. however,the incidence of swd was markedly reduced either by the 5-ht1a agonist (±)-8-hydroxy-2-(di-n-propylamino)-tetralin [(±)8-oh-dpat] or the 5-ht2 agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)doi]. the 5-ht reuptake inhibitors,fluoxetine and clomipramine,also inhibited the swd generation. in addition,the inhibitory effects of (±)8-oh-dpat and (±)doi were reversed by way-100135 (5-ht1a antagonist) and ritanserin (5-ht2 antagonist),respectively. the present results suggest that the serotonergic system negatively regulates the incidence of absence seizures by stimulation of 5-ht1a and 5-ht2 receptors. ©2010 the japanese pharmacological society.