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

Dec 10, 2017Neuropharmacology

The hallucinogen 5-MeO-DMT changes activity between thinking and relay brain areas in moving mice, involving specific serotonin receptors

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Abstract

5-MeO-DMT significantly altered oscillatory activity in the prefrontal and visual cortices of freely-moving mice.

Effects of 5-MeO-DMT on oscillatory activity were more pronounced in cortical areas than in the thalamus.
In 5-HT-R knockout mice, 5-MeO-DMT produced marked increases in delta power specifically in the visual cortex.
5-MeO-DMT enhanced beta band coherence across all examined brain areas.
The 5-HT-R antagonist WAY-100635 blocked most of the 5-MeO-DMT effects on oscillatory activity in knockout mice.
These findings suggest that the hallucinatory effects of 5-MeO-DMT may involve simultaneous changes in prefrontal and visual cortex activities.

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5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT/5-HTreceptor agonist. Its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. Moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. Our previous results in anesthetized animals show that 5-MeO-DMT alters cortical activity via 5-HTand 5-HTreceptors. Here, we examined 5-MeO-DMT effects on oscillatory activity in prefrontal (PFC) and visual (V1) cortices, and in mediodorsal thalamus (MD) of freely-moving wild-type (WT) and 5-HT-R knockout (KO2A) mice. We performed local field potential multi-recordings evaluating the power at different frequency bands and coherence between areas. We also examined the prevention of 5-MeO-DMT effects by the 5-HT-R antagonist WAY-100635. 5-MeO-DMT affected oscillatory activity more in cortical than in thalamic areas. More marked effects were observed in delta power in V1 of KO2A mice. 5-MeO-DMT increased beta band coherence between all examined areas. In KO2A mice, WAY100635 prevented most of 5-MeO-DMT effects on oscillatory activity. The present results indicate that hallucinatory activity of 5-MeO-DMT is likely mediated by simultaneous alteration of prefrontal and visual activities. The prevention of these effects by WAY-100635 in KO2A mice supports the potential usefulness of 5-HTreceptor antagonists to treat visual hallucinations. 5-MeO-DMT effects on PFC theta activity and cortico-thalamic coherence may be related to its antidepressant activity. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'. 1A2A1A2A2A1A1A

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

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