Serotonin depletion attenuates AY-9944-mediated atypical absence seizures.
OBJECTIVE
To test the hypothesis that serotonin (5-HT) plays a role in the modulation of experimental atypical absence seizures.


METHODS
Male Long-Evans hooded rats were treated from postnatal day (P) 2 to P20 with the cholesterol inhibitor AY-9944 (AY). Epidural electrodes were implanted for electrocorticography (ECoG) followed by serotonin depletion by using para-cholorophenylalanine (PCPA). High-performance liquid chromatography (HPLC) was used to measure the levels of serotonin and its metabolite (5-HIAA) in various brain regions. Serotonin metabolism was computed by using the 5-HIAA/5-HT ratio and used to ascertain differences between groups.


RESULTS
PCPA treatment was associated with a significant decrease in the total slow spike-and-wave discharge (SSWD) duration in AY-treated rats compared with controls (p < 0.01). HPLC data confirmed the PCPA depletion of 5-HT and 5-HIAA in cortex, thalamus, hippocampus, and brainstem compared with naïve rats. AY-treated rats showed higher levels of 5-HIAA and 5-HT in the same brain regions, with a concomitant decrease in rates of serotonin turnover.


CONCLUSIONS
The data indicate that serotonin depletion protects against experimental atypical absence seizures. The increased levels of 5-HIAA and 5-HT and altered rates of serotonin turnover suggest that the serotonergic neurotransmission may be perturbed in the AY rat.
Bercovici
Eduard
E
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Cortez
Miguel A
MA
Wang
Xiaomei
X
Snead
O Carter
OC
D000818:Animals; D000924:Anticholesteremic Agents; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D004832:Epilepsy, Absence / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D010134:Fenclonine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride
D000924:Anticholesteremic Agents; D012702:Serotonin Antagonists; D012701:Serotonin; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride; D006897:Hydroxyindoleacetic Acid; D010134:Fenclonine