Abstract
The plant cannabinoid Δ9-tetrahydrocannabinol and the endocannabinoid anandamide increase the amount of sleep via a CB1 receptor mediated mechanism. Here, we explored the use of a novel electroencephalogram (EEG) recording device based on wireless EEG microchip technology (Neurologger) in freely-moving rats, and its utility in experiments of cannabinoids-induced alterations of EEG/vigilance stages. EEG was recorded through epidural electrodes placed above pre-frontal and parietal cortex (overlaying the dorsal hippocampus). As cannabinoids, we acutely administered the full synthetic CB1 receptor agonist, WIN55,212-2 (1 mg/kg), and the antagonist/inverse agonist, AM251 (2 mg/kg), either alone or together through the intraperitoneal route. WIN55,212-2 increased the total amount of NREM sleep and the length of each NREM bout, but this was unlikely due to CB1 receptor activation since it was not prevented by AM251. However, WIN55,212-2 also lowered overall EEG spectral power especially in theta and alpha frequency bands during wakefulness and NREM sleep, and this effect was reversed by AM251. The antagonist/inverse agonist caused no sleep alterations by itself and moderately increased spectral power in Theta, alpha and beta frequency bands during NREM sleep when administered on its own. Implications of endocannabinoid modulation of the sleep-wake cycle and its possible interactions with other transmitter systems are considered.
Highlights
It is widely known that the active ingredient of marijuana, Δ9-Tetrahydrocannabinol (Δ9-THC), modulates the sleepwake cycle
The main objective here was to pharmacologically characterize the acute effects of the full CB1 receptor agonist WIN 55,212-2 (WIN-2) on sleep. This is of particular interest since we have previously reported WIN-2 to impair memory formation in spatial learning tasks [15,16,17], and these deficits are reversible by CB1 receptor antagonist/inverse agonist such as AM251
The AM251-related increase in spectral power in theta, alpha, and beta bands during NREM was not reversed in the presence of WIN-2 in the hippocampus, which suggests that these changes were not mediated by CB1 receptors
Summary
It is widely known that the active ingredient of marijuana, Δ9-Tetrahydrocannabinol (Δ9-THC), modulates the sleepwake cycle. Santucci and coworkers [8] were the first to study the physiological role of endocannabinoids on sleep They systemically administered the CB1 receptor antagonist/inverse agonist, SR141716A (SR), to rats and observed a dose-dependent increase in wakefulness (W) and a reduction in both slowwave (SWS) and rapid eye movement (REM) sleep. This indicated that the wake-promoting properties of SR arise as a result of the inhibition of the endocannabinoid tone on CB1 receptors [9] and/or due to an inverse agonism [10, 11] on the same subset of G-protein coupled receptors. We here adapted the system to rat in a proof-of-principle pilot study and at the same time explored the possibility to reduce the number of subjects by repeatedly monitoring drug effects in a longitudinal fashion in freely moving rats
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