title: The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.
abstract: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona,Spain.
authors.forename: Maurizio S
authors.initials: MS
authors.lastname: Riga
authors.affiliation: Experimental 7T MRI Unit,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona,Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Soria
authors.affiliation: Experimental 7T MRI Unit,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona,Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Tudela
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona,Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Artigas
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona,Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Celada
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D031581:Banisteriopsis / Q000737:chemistry*; D058256:Brain Waves / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D059907:Functional Neuroimaging; D006213:Hallucinogens / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008732:Methoxydimethyltryptamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018967:Risperidone / Q000494:pharmacology; D014793:Visual Cortex / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology
chemical_list: D000596:Amino Acids; D014150:Antipsychotic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D006213:Hallucinogens; C118218:LY 379268; D008732:Methoxydimethyltryptamines; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone