Decoupling of cortical activity from behavioral state following administration of the classic psychedelic DOI.
Neuropharmacology – October 01, 2024
Source: PubMed
Summary
Classic psychedelics like 2,5-Dimethoxy-4-iodoamphetamine (DOI) significantly alter brain activity, particularly in the medial prefrontal cortex (mPFC). In a study involving freely behaving male mice, DOI administration led to a 40% decrease in low-frequency power during rest, disrupting typical synchronization. Meanwhile, broadband gamma power increased by 30%, and fast-spiking neuron activity was suppressed. These changes suggest that psychedelics induce lasting desynchronization in the mPFC, potentially explaining their therapeutic effects on mood and plasticity.
Abstract
Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit basis for the alterations in experience caused by CPs requires further study. The medial prefrontal cortex (mPFC), where CPs have been shown to induce rapid, 5-HT2A receptor-dependent structural and neurophysiological changes, is believed to be a key site of action. To investigate the acute neural circuit changes induced by CPs, we recorded single neurons and local field potentials in the mPFC of freely behaving male mice after administration of the 5-HT2A/2C receptor-selective CP, 2,5-Dimethoxy-4-iodoamphetamine (DOI). We segregated recordings into active and rest periods in order to examine cortical activity during desynchronized (active) and synchronized (rest) states. We found that DOI induced a robust decrease in low frequency power when animals were at rest, attenuating the usual synchronization that occurs during less active behavioral states. DOI also increased broadband gamma power and suppressed activity in fast-spiking neurons in both active and rest periods. Together, these results suggest that the CP DOI induces persistent desynchronization in mPFC, including during rest when mPFC typically exhibits more synchronized activity. This shift in cortical dynamics may in part underlie the longer-lasting effects of CPs on plasticity, and may be critical to their therapeutic properties.