Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents

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 h 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 h after lysergic acid diethylamide (LSD) administration would lead to different effects than brain stimulation alone. Methods: We recorded local field potential oscillations from rats after LSD or saline (SAL) administration and determined whether exposure to these treatments altered the effect of a targeted intervention (brain stimulation) 24 h 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 h. Brain stimulation applied in the previously reported window of heightened neuroplasticity produced distinct shifts in brain state compared with brain stimulation applied 24 h after SAL administration. Conclusions: Despite the acute effects of LSD disappearing after 24 h, there are still latent effects that interact with brain stimulation to create larger and distinct changes in brain activity compared with 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 study will assess impacts on stimulation-induced changes in behavior.