Differential Effect of Serotonin Depletion in Two Experimental Absence Seizure Models
Abstract number :
1.254
Submission category :
Year :
2001
Submission ID :
2850
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
M.A. Cortez, MD., Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada; E. Bercovici, BSc., Neuroscience Program, University of Toronto, Toronto, ON, Canada; J.W. Dailey, Ph.D., Department of Biomedical and Therapeutic Sciences, Univ
RATIONALE: To establish whether serotonergic mechanisms regulate and differentiate experimental typical (1) from atypical absence seizures (2).
METHODS: Fifty four adult rats with implanted epidural electrodes were treated with carbamazepine (CBZ)(32mg/kg), Phenytoin (PHT)(100mg/kg), Ethosuximide (ETO), Methylcellulose (MET) or Arabic Gum (AG)(10%) for 1h EEG/Video recordings during [gamma]-hydroxybutyrate (GHB) or AY-9944 (AY) absence seizures, before and after parachlorophenylalanine (PCPA)(150mg/kg x 3 days). Baseline, pre-treatment and test recordings with 5-hydroxytryptophan (5-HTP)(50mg/kg) were ascertained to determine the latency to spike-and-wave discharge (SWD) and the brains removed for 5-HT determination.
RESULTS: PCPA decreased AY-SWD (Mean[plusminus]SEM) from 360.83 [plusminus]70.31 to 139.33[plusminus]38.21 seconds/h (p.[lt] 0.05). PCPA-ETO decreased SWD from 122.50[plusminus]60.96 to 49.17[plusminus]9.88 sec./h (p.=0.35). PCPA-CBZ decreased from 1941.80[plusminus]209.78 to 808.88[plusminus]343.61 sec./h (p.[lt]0.005). PCPA-AG increased SWD from 32.33[plusminus]14.30 to 42[plusminus]16.54 sec./h (p.=0.70). 5-HTP increased AY-SWD (1860[plusminus]209) compared to controls (p.[lt]0.05)(Student[ssquote]s t Test).
CONCLUSIONS: Data indicate that serotonergic mechanisms are involved only in experimental atypical absence seizures. PCPA either protects or potentiates the ictal manifestation depending on the seizure type. Serotonergic mechanisms may be critical in malignant atypical absence seizure regulation.
(1) Cortez MA et al. Exacerbation effect of CBZ of [gamma]hydroxybutyric acid induced SWD, is potentiated by depletion of serotonin in rats. Epilepsia 1998; 39(6):36.
(2) Cortez MA, McKerlie C, O. C Snead III. A model of Atypical Absence Seizures: EEG. Pharmacology and Developmental Characterization. Neurology 2001; 56:341-349.
Support: Supported in part by the Bloorview Children[ssquote]s Hospital Foundation, The Hospital for Sick Children Pediatric Consultants and The Canadian Institutes of Health Research.