Effects of Trace Amine-Associated Receptor 1 Agonists on Nicotine Abuse-Related Behaviors
Seaman, Robert W., Jr.
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Trace amine-associated receptor 1 (TAAR1) is a newly characterized G protein-coupled receptor that has been shown to modulate dopaminergic systems. Previous research has shown that the TAAR1 full agonist RO5166017 and the partial agonist RO5263397 exhibit pharmacological generalities in their abilities to modulate cocaine abuse-related behaviors in animal models. However, it is not known if these same compounds are able to modulate nicotine abuse-related behaviors. This thesis examined the effects of RO5166017 on the expression of nicotine-induced locomotor sensitization. Next, the ability of RO5263397 to alter nicotine self-administration was measured via an economic demand curve analysis. Finally, the ability of RO5166017 to attenuate cue- and nicotine-induced reinstatement of nicotine-seeking behavior was investigated. RO5166017 attenuated the expression of nicotine-induced locomotor sensitization. Behavioral economic analysis revealed that RO5263397 increased the elasticity of the nicotine demand curve along with decreasing consumption of nicotine at minimal response requirements. Lastly, RO5166017 attenuated cue- and nicotine-induced reinstatement of nicotine-seeking behavior. Taken together, these data suggest that TAAR1 modulates nicotine abuse-related behaviors and proves to be a potential novel target for future pharmacotherapies to treat nicotine addiction.