Impact of modulation of the α7 nicotinic acetylcholine receptor on nicotine reward in the mouse conditioned place preference test

Abstract

Rationale The α7 nicotinic acetylcholine receptor (nAChR) has been implicated as a target in modulating nicotine reward. However, the effect of pharmacological agents that have been shown to alter the channel properties of the α7 nAChR is not well understood in nicotine reward. Objectives This study aimed to investigate the impact of α7 nAChR pharmacological modulation on nicotine conditioned place preference (CPP) in mice by using positive allosteric modulators (PAMs) and a silent agonist. Methods The effect of the orthosteric α7 nAChR full agonist PNU282987 (1.3 and 9 mg/kg, s.c.), Type I α7 PAM NS1738 (1 and 10 mg/kg; i.p.), the Type II α7 PAM PNU120596 (0.3, 1, and 3 mg/kg, i.p.), and the α7 silent agonist NS6740 (1 and 3 mg/kg, i.p) on nicotine CPP was measured in mice. Mice were conditioned with either saline or nicotine (0.5 mg/kg) for 3 days in the CPP paradigm. Results The α7 full orthosteric agonist PNU282987 and the Type II α7 nAChR PAM PNU120596 reduced nicotine CPP, while the silent agonist NS6740 and Type I PAM NS1738 had no effect. The effects of PNU282987 and PNU120596 did not have an effect on morphine CPP. Conclusions Taken together, our results suggest that modulation of the α7 nAChR can play important roles in nicotine CPP in mice. In addition, the Type II α7 nAChR PAM PNU120596 attenuated nicotine reward suggesting that endogenous acetylcholine/choline tone is sufficient to reduce nicotine CPP. These findings highlight a beneficial effect of using α7 nAChR PAMs in nicotine reward.

Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission

“…We also assessed whether KP (30 mg/kg; i.p.) can trigger brain reward mechanisms by measuring conditioned place preference (CPP) 46,47 , and observed no such effects (Supplementary Fig. 3d).…”

Negative and positive allosteric modulators of the α7 nicotinic acetylcholine receptor regulates the ability of adolescent binge alcohol exposure to enhance adult alcohol consumption

“…Enhancing KYNA levels in the brain prevents nicotine-induced increases in dopamine (Erhardt et al, 2001 ) and glutamate (Konradsson-Geuken et al, 2009 ), reduces the reinforcing properties of Tetrahydrocannabinol (THC) (Justinova et al, 2013 ), and reduces nicotine craving and relapse (Secci et al, 2017 ). Although α7 PAMs have been reported to reduce the reinforcing properties of nicotine (Jackson et al, 2019 ), complete dose-response analyses have indicated that α7 PAMs produce leftward-shifts (increase sensitivity) in the dose-response curve for nicotine reward behaviors (Perkins et al, 2018 ). Recent clinical data have indicated that treatment with an α7 PAM increased nicotine craving and nicotine use (Perkins et al, 2018 ).…”

Repurposing cell growth-regulating compounds identifies kenpaullone which ameliorates pathologic pain via normalization of inhibitory neurotransmission

“…We also tested whether KP (30 mg/kg; i.p.) can trigger brain reward mechanisms by assessing conditioned place preference (Jackson et al, 2019;Sora et al, 1998), and there were no such effects ( Fig. 2E).…”