BACKGROUND AND PURPOSE: The endocannabinoid system appears to play a pivotal role in mediating the rewarding and reinforcing effects of nicotine. Recent studies have shown that the inhibition of fatty acid amide hydrolase (FAAH) attenuates reinstatement of nicotine-seeking induced by nicotine priming and nicotine-associated cues. FAAH hydrolyses the endogenous endocannabinoid anandamide, as well as other non-cannabinoid ligands such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). As OEA and PEA can attenuate both nicotine-taking and nicotine-seeking behaviour, the specific role of anandamide remains unclear. In this study, we have tested the selective anadamide uptake inhibitor, VDM11, which elevates anandamide levels without affecting levels of OEA/PEA, on nicotine-taking and nicotine-seeking behaviour. EXPERIMENTAL APPROACH: We used a nicotine intravenous self-administration model in rats to assess the effect of VDM11, given i.p., on nicotine taking using fixed and progressive ratio schedules of reinforcement as well as on reinstatement of nicotine-seeking induced by nicotine priming and nicotine-associated cues. KEY RESULTS: VDM11 did not affect levels of responding for nicotine under fixed-ratio and progressive-ratio schedules of reinforcement. In contrast, VDM11 dose-dependently attenuated reinstatement of nicotine-seeking behaviour induced by nicotine-associated cues and nicotine priming. CONCLUSIONS AND IMPLICATIONS: These results indicate that ligands elevating anandamide levels could have therapeutic value for preventing relapse into nicotine-seeking behaviour and should be tested in humans trying to quit smoking.
BACKGROUND AND PURPOSE: The endocannabinoid system appears to play a pivotal role in mediating the rewarding and reinforcing effects of nicotine. Recent studies have shown that the inhibition of fatty acid amide hydrolase (FAAH) attenuates reinstatement of nicotine-seeking induced by nicotine priming and nicotine-associated cues. FAAH hydrolyses the endogenous endocannabinoidanandamide, as well as other non-cannabinoid ligands such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). As OEA and PEA can attenuate both nicotine-taking and nicotine-seeking behaviour, the specific role of anandamide remains unclear. In this study, we have tested the selective anadamide uptake inhibitor, VDM11, which elevates anandamide levels without affecting levels of OEA/PEA, on nicotine-taking and nicotine-seeking behaviour. EXPERIMENTAL APPROACH: We used a nicotine intravenous self-administration model in rats to assess the effect of VDM11, given i.p., on nicotine taking using fixed and progressive ratio schedules of reinforcement as well as on reinstatement of nicotine-seeking induced by nicotine priming and nicotine-associated cues. KEY RESULTS:VDM11 did not affect levels of responding for nicotine under fixed-ratio and progressive-ratio schedules of reinforcement. In contrast, VDM11 dose-dependently attenuated reinstatement of nicotine-seeking behaviour induced by nicotine-associated cues and nicotine priming. CONCLUSIONS AND IMPLICATIONS: These results indicate that ligands elevating anandamide levels could have therapeutic value for preventing relapse into nicotine-seeking behaviour and should be tested in humans trying to quit smoking.
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