Abstract
Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity.
Highlights
Cannabis is the most widely used illicit drug in the world
Before the onset of these cannabis smoke exposure sessions, the air-control rats and the cannabis rats were tested in the small open field for 30 min
The studies showed that cannabis smoke increased locomotor activity when the rats were tested immediately after smoke exposure, but not when tested 4 h, 24 h or 48 h after cannabis smoke exposure
Summary
Cannabis is the most widely used illicit drug in the world. The United Nations Office on Drugs and Crime estimates that 2.7–4.9% of adults worldwide use cannabis [1]. The prevalence of cannabis use is high in Ghana (21.5%), Zambia (17.7%), Canada (17.0%), the United States of America (12.3%), and New Zealand (13.3%)[2]. The subjective effects of cannabis and its main psychoactive component, delta-9-tetrahydrocannabinol (Δ9-THC), include relaxation, mild euphoria, perceptual changes, intense laughter, and talkativeness [3, 4]. Cannabis use can have adverse effects including impaired memory function and paranoia [5, 6]. There are currently no pharmacological treatments for cannabis addiction
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