The high frequency oscillation in orbitofrontal cortex is susceptible to phenethylamine psychedelic 25C-NBOMe in male rats.

The substituted phenethylamine psychedelic 25C-NBOMe, at a dose of 0.1 mg/kg that disrupts sensorimotor gating, selectively potentiates high frequency oscillation (HFO, 120-150 Hz) power in the orbitofrontal cortex (OFC) of male Sprague-Dawley rats, peaking 20-30 minutes after treatment. It strengthens HFO coherence within the intra-prefrontal network but not the hippocampal-prefrontal network. Potentiated OFC HFO strongly correlates with strengthened inter-prefrontal HFO coherence. Pre-treatment with the serotonin 2A receptor antagonist MDL100,907 prevents these alterations. The findings indicate that OFC HFO is particularly susceptible to this psychedelic and may drive drug-induced rhythmic coherence within prefrontal regions, suggesting altered HFO could serve as a biological marker of psychedelic effects.

Study at a glance

Abstract

Serotoninergic psychedelics induced extensive alterations in perception and cognition, which has been attributable to its disruptive effect on oscillatory rhythms of prefrontal cortex. However, there is a lack of information how serotoninergic psychedelics affect the intra-prefrontal network, which intrinsically interact to accomplish perceptual processing. Uncovering the altered neural network caused by psychedelics helps to understand the mechanisms of their psychoactive effects and contribute to develop biological markers of psychedelic effects. In present study, we investigated the effects of substituted phenethylamine psychedelic 25C-NBOMe on neural oscillations in the intra-prefrontal and hippocampal-prefrontal network. The effective dose of 25C-NBOMe (0.1 mg/kg) disrupting sensorimotor gating in male Sprague-Dawley rats was used to observe its effects on neural oscillations in the prelimbic cortex, anterior cingulate cortex, orbitofrontal cortex (OFC) and hippocampus CA1. The power of high frequency oscillation (HFO, 120-150 Hz) was potentiated by 25C-NBOMe selectively in the OFC, with peaking at 20-30 min after treatment. 25C-NBOMe strengthened HFO coherence within the intra-prefrontal, rather than hippocampal-prefrontal network. Potentiated HFO in the OFC had a strong positive correlation with the strengthened inter-prefrontal HFO coherence by 25C-NBOMe. The 25C-NBOMe-induced alterations of rhythmic patterns were prevented by pre-treatment with selective serotonin 2A receptor antagonist MDL100,907. These results demonstrate that OFC rhythmic activity in HFO is relatively susceptible to substituted phenethylamine and potentially drives drug-induced rhythmic coherence within intra-prefrontal regions. Our findings provide additional insight into the neuropathophysiology of the psychoactive effects of psychedelics and indicate that the altered HFO might be applied as a potential biological marker of psychedelic effect.