|Title / Titel||Effect of the mixed 5-HT2/6 and D2 antagonist sertindole on NMDA antagonist-induced sensory gating and cognition deficts in healthy humans|
|Abstract (PDF, 14 KB)|
|Summary / Zusammenfassung||The psychotomimetic NMDA antagonist such as S-ketamine mimic both positive and negative symptoms as well as some cognitive deficts of schizophrenia in healthy humans. In animals, NMDA antagonict also disrupt sensorgy gating (PPI) which may render schizophrenia patients to become oberloaded with excessive exteroceptive and interoceptive stimuli which in turn could lead to a break down of cognitive integrity. More recently it has been demonstrated that NMDA antagonist-induced PPI and cognitive deficits in rodedens are ameliorated by mixed 5-HT2/D2 and 5-HT2/6 antagonists suggesting a role for the serotnin system in schizophrenia.
This study aims at investigatin whether the novel 5-HT2/5-HT6 and D2 antagonist sertindole reverses ketamine-induced alterations in sensory gating and associated psychopathology and cognitive deficts in healthy human This goal shall be accomplished by investigating the effect of sertindole on prepulse inhibition of the acoustic startle (PPI) and its relation to cognitive performance (attentional set-shifting, working memory, visual memory, and executive functioning) before and after treament with S-ketamine. The study shall help to elucidate whether atypical antipsychotic that are antagonists at 5-HT2 and %HT6 repeceptors might be superior over classic atypical antipsychotics (5-HT2/D2) in reducing cognitive impairments in the NMDA model of psychosis. Such differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance.
|Keywords / Suchbegriffe||sensory gating, PPI, NMDA, ketamine, cognition, sertindole, antipsychotics, schizophrenia|
|Project leadership and contacts /
Projektleitung und Kontakte
|Funding source(s) /
|Foundation, Private Sector (e.g. Industry)
|Duration of Project / Projektdauer||Jan 2008 to Mar 2013|