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-HT(1A) and 5-HT(2) agonists on the incidence of spike-and-wave discharges (SWD) in Groggy (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-HT(1A) agonist (±)-8-hydroxy-2-(di-n-propylamino)-tetralin [(±)8-OH-DPAT] or the 5-HT(2) 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-HT(1A) antagonist) and ritanserin (5-HT(2) antagonist), respectively. The present results suggest that the serotonergic system negatively regulates the incidence of absence seizures by stimulation of 5-HT(1A) and 5-HT(2) receptors.
Ohno
Yukihiro
Y
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan. yohno@gly.oups.ac.jp
Sofue
Nobumasa
N
Imaoku
Takuji
T
Morishita
Eri
E
Kumafuji
Kenta
K
Sasa
Masashi
M
Serikawa
Tadao
T
D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D051381:Rats; D011922:Rats, Mutant Strains; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D044282:Receptor, Serotonin, 5-HT1A; D044348:Receptors, Serotonin, 5-HT2; D012701:Serotonin; D017366:Serotonin Receptor Agonists; C491367:Cacna1a protein, rat; D020864:Calcium Channels, N-Type