5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system.
Communications biology – July 26, 2023
Source: PubMed
Summary
Different psychedelic compounds create remarkably similar brain wave patterns, despite working through distinct chemical pathways. Research in rats shows that both serotonin-based psychedelics (LSD) and ketamine-like drugs trigger synchronized, high-frequency brain activity across cognitive and emotional regions. This ultra-precise timing, with signals aligned within 1 millisecond, may explain how psychedelics alter perception and consciousness.
Abstract
The profound changes in perception and cognition induced by psychedelic drugs are thought to act on several levels, including increased glutamatergic activity, altered functional connectivity and an aberrant increase in high-frequency oscillations. To bridge these different levels of observation, we have here performed large-scale multi-structure recordings in freely behaving rats treated with 5-HT2AR psychedelics (LSD, DOI) and NMDAR psychedelics (ketamine, PCP). While interneurons and principal cells showed disparate firing rate modulations for the two classes of psychedelics, the local field potentials revealed a shared pattern of synchronized high-frequency oscillations in the ventral striatum and several cortical areas. Remarkably, the phase differences between structures were close to zero, corresponding to <1 ms delays. Likely, this hypersynchrony has major effects on the integration of information across neuronal systems and we propose that it is a key contributor to changes in perception and cognition during psychedelic drug use. Potentially, similar mechanisms could induce hallucinations and delusions in psychotic disorders and would constitute promising targets for new antipsychotic treatments.