am4113 and Weight-Loss

Multiple studies suggest a pivotal role of the endocannabinoid system in regulating the reinforcing effects of various substances of abuse. Rimonabant, a CB. Rats were trained to self-administer nicotine under a fixed-ratio 5 or progressive-ratio schedules of reinforcement. A control group was trained to self-administer food. The acute/chronic effects of AM4113 pretreatment were evaluated on nicotine taking, motivation for nicotine, and cue-, nicotine priming- and yohimbine-induced reinstatement of nicotine-seeking. The effects of AM4113 in the basal firing and bursting activity of midbrain dopamine neurons were evaluated in a separate group of animals treated with nicotine. Anxiety/depression-like effects of AM4113 and rimonabant were evaluated 24h after chronic (21 days) pretreatment (0, 1, 3, and 10mg/kg, 1/d).. AM4113 significantly attenuated nicotine taking, motivation for nicotine, as well as cue-, priming- and stress-induced reinstatement of nicotine-seeking behavior. These effects were accompanied by a decrease of the firing and burst rates in the ventral tegmental area dopamine neurons in response to nicotine. On the other hand, AM4113 pretreatment did not have effects on operant responding for food. Importantly, AM4113 did not have effects on anxiety and showed antidepressant-like effects.. Our results indicate that AM4113 could be a promising therapeutic option for the prevention of relapse to nicotine-seeking while lacking anxiety/depression-like side effects.

Topics: Animals; Anxiety; Behavior, Addictive; Behavior, Animal; Cannabinoid Receptor Antagonists; Cues; Depression; Disease Models, Animal; Dopaminergic Neurons; Dose-Response Relationship, Drug; Drug Inverse Agonism; Drug-Seeking Behavior; Male; Maze Learning; Mesencephalon; Motivation; Motor Activity; Piperidines; Pyrazoles; Rats, Long-Evans; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; Signal Transduction; Swimming; Time Factors; Tobacco Use Cessation Devices; Tobacco Use Disorder; Weight Loss