期刊
NEUROPHARMACOLOGY
卷 101, 期 -, 页码 370-378出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2015.10.016
关键词
Prefrontal cortex; Sensorial cortical areas; Visual cortex; Hallucinogens; 5-HT receptors; Oscillatory activity
资金
- Instituto de Salud Carlos III (PN de I+D+I, ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion - European Regional Development Fund) [PI09/1245, PI12/00156, PI13/01390]
- Spanish Ministry of Economy and Competitiveness [SAF 2012-35183]
- European Regional Development Fund (ERDF)
- Centro de Investigacion Biomedica en Red de Salud Mental [CIBERSAM P82, 11INT3]
- Innovative Medicines Initiative Joint Undertaking (IMI) [115008]
- Generalitat de Catalunya [2014 SGR798]
- IDIBAPS fellowship
- Lundbeck
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen, acting as a non-selective serotonin 5-HT1A/5-HT2A-R agonist. Psychotomimetic agents such as the non-competitive NMDA-R antagonist phencyclidine and serotonergic hallucinogens (DOI and 5-MeO-DMT) disrupt cortical synchrony in the low frequency range (<4 Hz) in rat prefrontal cortex (PFC), an effect reversed by antipsychotic drugs. Here we extend these observations by examining the effect of 5-MeO-DMT on low frequency cortical oscillations (LFCO, <4 Hz) in PFC, visual (V1), somatosensory (Si) and auditory (Au1) cortices, as well as the dependence of these effects on 5-HT1A-R and 5-HT2A-R, using wild type (WT) and 5-HT2A-R knockout (KO2A) anesthetized mice. 5-MeO-DMT reduced LFCO in the PFC of WT and KO2A mice. The effect in KO2A mice was fully prevented by the 5-HT1A-R antagonist WAY-100635. Systemic and local 5-MeO-DMT reduced 5-HT release in PFC mainly via 54-IT1A-R. Moreover, 5-MeO-DMT reduced LFCO in Si, Au1 and V1 of WT mice and only in V1 of KO2A mice, suggesting the involvement of 5-HT1A-R activation in the 5-MeO-DMT-induced disruption of V1 activity. In addition, antipsychotic drugs reversed 5-MeO-DMT effects in WT mice. The present results suggest that the hallucinogen action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory (Si, Au1, V1) and associative (PFC) cortical areas, also supporting a role of 5-HT1A-R stimulation in V1 and PFC, in addition to the well-known action on 5-HT2A-R. Moreover, the reversal by antipsychotic drugs of 5-MeO-DMT effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development. (C) 2015 Elsevier Ltd. All rights reserved.
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