Endocannabinoid Modulation of Sleep-Wake Dynamics

Authors

• MJ Pava
• DM Lovinger

Abstract

Medicinal marijuana is frequently touted as beneficial for sleep, but the data supporting this claim are weak. Nevertheless, preclinical evidence suggests that synthetic cannabinoid 1 receptor (CB1) agonists do facilitate time spent in non-rapid eye movement (NREM) sleep and reduce wake. While there are relatively few preclinical studies characterizing endocannabinoid regulation of sleep-wake states, given that sleep has been tightly linked to synaptic plasticity and metabolic processes, it seems likely that the endocannabinoid (EC) system would be involved in sleep processes. To investigate cannabinoid/endocannabinoid modulation of sleep, we used a set of pharmacological tools to thoroughly examine the influence of endocannabinoid signaling in modulating neural circuits important for sleep-wake dynamics. In the process of this work, we have created and validated additional computational tools for performing rapid, fully-automated scoring and analysis of electrographic measures of global brain states (electrocorticogram and electromyogram). In addition, we have developed cheap and effective hardware for performing sleep-deprivation experiments in mice using forced locomotion via the rotating disc paradigm. The results of these studies indicate that increasing signaling through the CB1 receptor facilitates sleep by increasing the stability of NREM. In contrast, CB1 antagonism fragments sleep but only slightly impairs the rebound in NREM following sleep deprivation. We conclude from these studies that the EC system is not an essential factor regulating sleep homeostasis per se, but it is important for regulating NREM stability. Consequently, we are developing a stochastic model of sleep-wake dynamics to directly assess kinetic parameters associated with vigilance state transitions/stability.

Scientific Focus Area: Neuroscience

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