Abstracts

Serotonergic mechanisms are involved in experimental atypical absence seizures [Epilepsia 2001; 42, (7): 81]. Baclofen acutely induces spike and wave discharges similar to AY-9944. PCPA and 5-HTP are known to attenuate and exacerbate AY seizures respectively. We set out to investigate the serotonin modulation of GABAB mediated mechanism of atypical absence seizures [Neurology 2001; 56:341- 349].
ECoG recordings before and after PCPA treatment (150 mg/kg x 3 days) or distilled water vehicle in na[iuml]ve Long Evans hooded rats (n= 10) and AY rats (n= 10) at postnatal day (P) 55. PCPA and 5-HTP (50 mg/kg) treated na[iuml]ve were challenged with Baclofen (2.5 mg/kg). AY rats were administered either PCPA or 5-HTP (50 mg/kg). Spike-wave discharges (SWD) were quantified in 20 minute epochs. All animals were kept under a controlled 12L-12D cycle, with lights on at 6 AM.
PCPA decreased AY- SWD (Mean seconds/hour [plusmn] SEM) from 484.42 [plusmn] 63.98 to 252.42 [plusmn] 13.48 seconds/hour (p [lt] 0.01) (Student[apos]s t Test). 5-HTP increased AY-SWD (1860.80[plusmn]209) compared to control AY (p[lt] 0.05). PCPA produced no significant effects in na[iuml]ve rats challenged with Baclofen (137.5 vs. 137.75). After 5-HTP or distilled water, Baclofen produced equal increase in SWD (227% and 225%).
Data suggest that serotonin may exacerbate AY-9944 mediated SWD through non-GABAB mechanisms. The precise mechanism by which serotonin exacerbates chronic atypical absence seizures remains to be determined.
[Supported by: Canadian Institutes of Health Research
Hospital for Sick Children Pediatric Consultants]