5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system.
Ivani Brys, Sebastian A Barrientos, Jon Ezra Ward, Jonathan Wallander, Per Petersson, Pär Halje
Communications biology July 26, 2023 DOI: 10.1038/s42003-023-05093-6 via PubMed
Summary
AI-generated from the abstractPsychedelics like LSD, DOI, ketamine, and PCP produce profound changes in perception and cognition by inducing synchronized high-frequency oscillations across multiple brain regions. In rats, these drugs caused near-zero phase delays (<1 ms) in the ventral striatum and cortical areas, indicating hypersynchrony that likely disrupts information integration across neural systems. This shared pattern, despite different firing rate effects on interneurons and principal cells, suggests a key mechanism behind altered states of consciousness. Similar hypersynchrony may contribute to hallucinations and delusions in psychotic disorders, offering potential targets for new antipsychotic treatments.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Freely behaving rats |
| Interventions | LSD DOI ketamine PCP |
| Keywords | Neuroscience Psychedelics Brain waves Consciousness Pharmacology |
| Citations | 33 |
| Key finding | Psychedelics from two classes produce a shared pattern of synchronized high-frequency oscillations with near-zero phase delays across brain structures, likely contributing to altered perception and cognition. |
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.