|Title / Titel||Role of serotonin (5-HT2A and 5-HT1A) receptors in visual and emotional processing in normal and psilocybin-induced states of consciousness|
|Abstract (PDF, 14 KB)|
|Summary / Zusammenfassung||Recent evidence shows that serotonin-5-HT2A and 5-HT1A receptors are critical in the behavioural effects of hallucinogens in animals and humans. Evidence that the serotonin and glutamate systems are critical in psychotic symptom formation and the generation of cognitive impairment in schizophrenia stems from recent research of the molecular, pharmacological, and psychological effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) (Gray and Roth, 2007; Geyer et al., 2009; Winter, 2009; Gonzalez-Maeso and Sealfon, 2009; Aghajanian, 2009).
Previous work of our lab demonstrated that the visual disturbances induced by the mixed serotonin 5-HT 2AR/1AR agonist psilocybin in humans are primarily due to its agonist action at cortical 5-HT2A receptors (Kometer et al. 2010). Although recent data suggest that cortical 5-HT1A receptor may antagonize 5-HT2A receptor-induced behavioral phenomena in animals, its exact role in visual processing in humans is not known.
Recent evidence from animal research has shown that hallucinogenic 5-HT2A agonists such as psilocybin or LSD, and non-hallucinogenic 5-HT2A agonists such as lisuride or ergotamine, both differentially activate specific intracellular signalling pathways at the level of G(q/11) and G(i/0) subtype G proteins (Gonzalez-Maeso et al., 2008). In addition, nonhallucinogenic 5-HT2A agonists as well as hallucinogenic 5-HT2A agonists showed differential effects on electrophysiological response, behaviour, intracellular signalling and gene expression and the specific effects induced by hallucinogens could be blocked by non-hallucinogenic 5-HT2A agonists (Gonzalez-Maeso et al., 2008).
Taken together, these findings suggest that hallucinogen-induced psychosis in man may be due to activation of a specific 5-HT2A mediated intracellular pathway and offer a novel testable hypothesis on the molecular mechanism of action of hallucinogens in humans.
In this study we will propose new experimental approaches to further investigate the role of the 5-HT2A and 5-HT1A receptors in psychotic symptom formation, perceptual disturbances and emotional effects of hallucinogens that are also relevant in naturally occurring psychoses
To investigate the role of the 5-HT1A and 5-HT2A receptors in the mechanism of action of the short acting hallucinogen psilocybin in humans, the effects of the 5-HT1A agonist buspirone and the non-hallucinogenic 5-HT2A-agonists ergotamine and hydergine on psilocybin-induced subjective phenomena, visual and emotional processing and sensorimotor gating are investigated. Specifically, alterations in visual processing (visual modal object completion, Kanizsa) and emotional processing (Eckman Faces) are assessed using EEG-ERP technique. Subjective effects are assessed by applying psychometric questionnaires
|Keywords / Suchbegriffe||5-HT2AR, 5-HT1AR, visual and emotional processing, psilocybin, EEG-ERP|
|Project leadership and contacts /
Projektleitung und Kontakte
|Funding source(s) /
HRC; SNM (2013)
|In collaboration with /
In Zusammenarbeit mit
|Duration of Project / Projektdauer||Nov 2009 to Sep 2013|