Serotonin modulates AY-9944-induced atypical absence seizures via the 5-HT2A receptor activation.
Published: 2004
Language: eng
Number of pages: 132
Description: Postnatal administration of the cholesterol inhibitor AY-9944 (AY) to Long Evans Hooded rats results in chronic atypical absence seizures which are unprovoked, lifelong, recurrent, and frequent. The occurrence of slow spike and wave discharges (SSWD) and myoclonic jerks during sleep in AY-treated rats suggest a perturbation of the serotonergic system. Experiments manipulating serotonin at the global and receptor level were carried out to investigate its role in modulating AY seizures. Serotonin depletion using para-chlorophenylalanine (PCPA) attenuated total SSWD duration. Paradoxically, 5-hydroxytryptophan (5-HTP) also decreased total SSWD. The effect of 5-HTP has been attributed to activation of 5-HT2 receptors because DOI, a 5-HT2A/C agonist dose-dependently attenuated seizures. The effect of DOI was attributed to actions at the 2A subtype because mCPP, a 5-HT2C preferring agonist, did not reduce SSWD, whereas the 5-HT2A antagonist ketanserin exacerbated SSWD. These results indicate that serotonin modulates SSWD in the AY model via 5-HT2A receptor activation.
Notes: Adviser:  O. Carter Snead, III.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0789.

MICR copy on microfiche (2 microfiches).