Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents

Lysergic acid diethylamide (LSD) acutely reduces low-frequency electrical activity across the brain in rats, an effect that returns to normal after 24 hours. However, brain stimulation applied during a window of heightened neuroplasticity 24 hours after LSD produces larger and distinct changes in brain activity compared to stimulation after a placebo. This proof-of-concept finding suggests that psychedelic drugs may work in combination with brain stimulation to achieve enhanced effects on brain activity, with future work needed to assess impacts on behavior.

Study at a glance

Abstract

Abstract Background Psychedelic drugs 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, psychedelic drugs elicit neuroplastic processes 24 hours after administration, priming neural circuits for change. The acute effects of psychedelic drugs 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 psychedelic drugs. 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 the previously reported 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 interact with brain stimulation to create larger and distinct changes in brain activity compared to brain stimulation alone. Our proof-of-concept findings are the first to suggest that psychedelic drugs could work in combination with brain stimulation to achieve enhanced effects on brain activity and future work will assess impacts on stimulation induced changes in behavior.