Serotonin depletion attenuates AY-9944-mediated atypical absence seizures

Purpose: 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 naive 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.