The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors

Introduction

Riga and colleagues situate their study within growing interest in the neurobiology of serotonergic hallucinogens, both as tools to model psychotic symptoms and as potential therapeutics for mood and anxiety disorders. They note that indoleamine hallucinogens such as 5-MeO-DMT bind with high affinity to several serotonin receptors, notably 5-HT1A and 5-HT2A receptors, and that previous preclinical work has linked the psychotomimetic effects of these drugs to cortical 5-HT2A receptor activation. At the same time, oscillatory activity across cortico-thalamic networks is central to sensory processing and cognition, and is modulated by serotonin; alterations in these rhythms have been reported in psychiatric disorders and after psychotomimetic drug administration. Prior recordings in anaesthetised animals showed that 5-MeO-DMT reduces low-frequency cortical oscillations and alters pyramidal neuron discharge, with indications that 5-HT1A receptors contribute to these effects. The present study set out to characterise how 5-MeO-DMT affects local field potential oscillations and interregional coherence in medial prefrontal cortex (mPFC), primary visual cortex (V1) and mediodorsal thalamus (MD) of freely moving mice. The investigators specifically probed the relative involvement of 5-HT1A and 5-HT2A receptors by comparing wild-type (WT) and 5-HT2A receptor knockout (KO2A) mice and by using the 5-HT1A antagonist WAY-100635. The stated aims were to advance understanding of the neural basis of hallucinations and to identify potential targets for treatment, and to expand knowledge about serotonergic hallucinogen actions in brain regions relevant to mood disorders.