Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents

Abstract

Background: Psychedelics have resurged in neuroscience and psychiatry with promising success in psychedelic-assisted therapy for the treatment of anxiety, depression, and addiction. At the cellular level, psychedelics elicit neuroplastic processes 24 hours after administration, priming neural circuits for change. The acute effects of psychedelics are well characterized with functional imaging and neural oscillations showing an increase in the entropy of spontaneous cortical activity. Hypotheses: We hypothesized that cortical-striatal oscillations recorded in rats would confirm the effects of psychedelics. We also hypothesized that brain stimulation delivered 24 hours after LSD administration would lead to different effects than brain stimulation alone. Methods: We recorded local field potential (LFP) oscillations from rats following lysergic acid diethylamide (LSD) or saline administration and determined if exposure to these treatments altered the effect of a targeted intervention (brain stimulation) 24 hours later. Results: We confirmed acutely decreased low frequency power across the brain when rats are given LSD. We also demonstrated these altered states return to baseline after 24 hours. Brain stimulation applied in this window of heightened neuroplasticity produced distinct shifts in brain state compared to brain stimulation applied 24 hours after saline. Conclusions: Despite the acute effects of LSD disappearing after 24 hours, there are still latent effects that synergize with brain stimulation to create different changes in brain activity compared to brain stimulation alone. Our findings are the first to suggest that psychedelics could have a role clinically in combination with brain stimulation to achieve enhanced effects on brain activity and clinical outcomes.

“Paradoxical wakefulness” induced by psychedelic 5-methoxy-N,N-dimethyltryptamine in mice

“…50 These findings, taken together with the proposed role of the 5-HT system in arousalpromotion, may suggest that the suppression of PS induced by psychedelic drugs is due to an acute disruption of the core mechanism of global vigilance state control. However, it has also been noted that administration of psychedelic drugs results in disrupted and desynchronised 4 EEG, [50][51][52][53] indicating that it is not merely global state control which is affected by psychedelics but also state quality. Surprisingly, the possibility that psychedelic drugs cause the occurrence of an altered state of vigilance has received less attention.…”