title: Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.
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.
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.|Department of Neuroscience, University of Florida, Gainesville, Florida, United States of America.|Center for Addiction Research and Education, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Adriaan W
authors.initials: AW
authors.lastname: Bruijnzeel
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Lidia V
authors.initials: LV
authors.lastname: Guzhva
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Shannon
authors.initials: S
authors.lastname: Wall
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.|Center for Addiction Research and Education, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Jie V
authors.initials: JV
authors.lastname: Deng
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gold
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.|Department of Neuroscience, University of Florida, Gainesville, Florida, United States of America.|Center for Addiction Research and Education, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.|Department of Neuroscience, University of Florida, Gainesville, Florida, United States of America.|Center for Addiction Research and Education, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Barry
authors.initials: B
authors.lastname: Setlow
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004361:Drug Tolerance; D063388:Endocannabinoids / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D002189:Marijuana Abuse / Q000209:etiology; D008385:Marijuana Smoking / Q000503:physiopathology*; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide