Vollenweider Andel
Fakultäten » Medizinische Fakultät » Psychiatrische Universitätsklinik » Affektive Erkrankungen und Allgemeinpsychiatrie Zürich Ost, Klinik für » Prof. Dr. Daniel Hell (emeritiert) » Vollenweider Andel
Completed research project
| Title / Titel | Cortical organisation and the role of serotonin-2A receptors in the NMDA antagonist model of cognitive deficits: A H215O-PET study in healthy human volunteers | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | N-methyl-D-aspartate (NMDA) receptor antagonists such as S-ketamine disrupt information processing in animals and produce cognitive deficits in healthy human volunteers similarly to those seen in schizophrenic psychoses (Geyer 1998, Umbricht et al. 2000, 2002). Moreover, extensive pharmacological studies in animals and neuroimaging studies in humans suggest that S-ketamine may produce these cognitive deficits in humans via disruption of glutamatergic NMDA, dopaminergic D2, and/or serotoninergic 5-HT2A receptor-mediated neurotransmission within cortico-striato-thalamic circuitry (Vollenweider and Geyer 2001). By elucidating the neuronal substrates of S-ketamine-induced cognitive impairments in normals and the impact of 5-HT2/D2 and 5-HT2A receptor antagonism on ketamine-induced psychosis, it might be possible to obtain critical information about the cortical organisation and the role of these receptors in schizophrenic psychoses. Thus, the first aim of this project is to localize the functional neuroanatomy underlying ketamine-induced attentional deficits by means of H215O-PET in normal human adults. This aim will be accomplished by comparing regional brain activation produced by moderate doses of S-ketamine during an attentional task (RVP task of the CANTAB battery) with those produced under placebo conditions. A second aim is to explore the role of 5-HT2A receptors in S-ketamine-induced attentional deficits by investigating the effect of the selective 5-HT2A antagonist ketanserin on S-ketamine-induced regional brain activity using H215O-PET. Finally, these data shall be compared in a parallel study in normals receiving the mixed 5-HT2/D2 antagonist clozapine. |
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| Publications / Publikationen | Vollenweider FX. (2001): Brain mechanisms of hallucinogens and entactogens. Dialogues in clinical neuroscience, 3: 265-279.Umbricht D, Schmid L, Koller R, Vollenweider FX, Hell D, Javitt DC (2000): Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers. Arch. Gen. Psychiatry, 57: 1139-1147.Umbricht D, Koller R, Vollenweider FX, Schmid L (2002): Mismatch negativity predicts psychotic experiences induced by NMDA receptor antagonist in healthy volunteers. Biol. Psychiatry, 51: 400-406. | ||||
| Keywords / Suchbegriffe | schizophrenia, attention, attentional deficits, ketamine, S-ketamine, 5-HT2, ketanserin, clozapine, positron emission tomography, PET, glutamate, serotonin, dopamine | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung), Foundation Foundation of Hope, Raleigh, NC USA |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Apr 2004 to Jun 2008 |