The Influence of Serotonergic Modulation on Auditory Evoked Potentials; Mismatch Negativity a Potential Translational Assay in Schizophrenia
Translated title
Indvirkningen af serotonerg modulering på auditive evokerede potentialer; Mismatch negativitet en potentiel translationel metode i skizofreni
Author
Birknow, Michelle Rosgaard
Term
4. term
Publication year
2011
Submitted on
2011-06-01
Abstract
Schizophrenia is a severe disorder, and there is a need for objective, translational measures of disease mechanisms. Mismatch negativity (MMN) is a brain response to unexpected sounds that is often reduced in schizophrenia and not normalized by antipsychotics. Because the selective serotonin reuptake inhibitor escitalopram can enhance MMN in healthy volunteers, this thesis examined whether increasing serotonergic activity modulates an MMN‑like response in rats and whether loudness dependence of auditory evoked potentials (LDAEP) serves as a marker of serotonergic activity. In freely moving rats, auditory evoked potentials were recorded from hippocampus and parietal cortex during an oddball paradigm with standard and deviant tones; LDAEP was assessed using increasing sound intensities. Escitalopram 3 mg/kg significantly increased the MMN‑like response in hippocampus, whereas combining escitalopram with the 5‑HT3 antagonist ondansetron produced no additional effect. LDAEP could not be validated as a reliable indicator of hippocampal serotonergic activity. These findings back‑translate human observations, support serotonergic modulation of MMN‑like signals in rats, and highlight MMN as a useful translational tool in schizophrenia research, while LDAEP did not appear suitable in this setting.
Skizofreni er en alvorlig lidelse, og der er behov for objektive, oversættelige mål for sygdomsmekanismer. Mismatch negativitet (MMN) er en hjerneaktivitet udløst af uventede lyde og er ofte nedsat ved skizofreni, mens antipsykotika ikke normaliserer den. Da den selektive serotoningenoptagshæmmer escitalopram kan øge MMN hos raske, undersøgte denne afhandling, om øget serotonerg aktivitet påvirker et MMN‑lignende respons hos rotter, og om loudness dependence of auditory evoked potentials (LDAEP) kan bruges som markør for serotonerg aktivitet. I fritgående rotter blev auditorisk fremkaldte potentialer registreret fra hippocampus og parietal cortex under et oddball‑paradigme med standard‑ og afvigende toner; derudover blev LDAEP testet med stigende lydstyrker. Escitalopram 3 mg/kg øgede signifikant det MMN‑lignende respons i hippocampus, mens kombination med 5‑HT3‑antagonisten ondansetron ikke gav en yderligere effekt. LDAEP kunne ikke valideres som en robust indikator for serotonerg aktivitet i hippocampus. Fundene støtter, at serotonerg modulering kan påvirke MMN‑lignende signaler i rotter og peger på MMN som et brugbart translationsværktøj i skizofreniforskning, mens LDAEP ikke fremstod egnet i denne opsætning.
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