Abstract
Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2) have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio) and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg) and CB2 agonist AM1241 (1 to 10 mg/kg) on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.
Highlights
Cigarette smoking is responsible for 5 million deaths worldwide every year
The cannabinoid system consists of CB1 and CB2 receptors, the endogenous cannabinoid receptor ligands, anandamide, and 2-arachidonoylglycerol (2-AG) [2,3], in addition to the enzymes responsible for their degradation which are fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase 2-AG, respectively [2,4]
This study is the first to evaluate the impact of selective CB2 receptor ligands on an animal model of nicotine-taking and nicotine-seeking behavior
Summary
Cigarette smoking is responsible for 5 million deaths worldwide every year. The mechanisms underlying tobacco smoking are of wide interest and clearly there is still a need for more effective medications to help in smoking cessation and prevent relapse [1]. The cannabinoid system appears to play a critical role in mediating the reinforcing effects of nicotine as well as relapse to nicotine-seeking behaviour. The cannabinoid system consists of CB1 and CB2 receptors, the endogenous cannabinoid receptor ligands, anandamide, and 2-arachidonoylglycerol (2-AG) [2,3], in addition to the enzymes responsible for their degradation which are fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase 2-AG, respectively [2,4]. The CB1 receptor is highly expressed in the CNS, and is considered the most abundant G protein coupled receptor in the brain [5]. Cannabinoids act at CB1 receptors located presynaptically to elicit changes in the synaptic efficacy of central neuronal circuits that are involved in several processes including reward [6]
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