Reduction in delay discounting due to nicotine and its attenuation by cholinergic antagonists in Lewis and Fischer 344 rats
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Nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs), and mecamylamine, a nonselective nAChR antagonist, attenuates effects of nicotine on delay discounting in some rat strains; whether nicotine’s attenuation is specific to nAChR antagonism is unknown.
During experiment 1, we evaluated dose-dependent effects of nicotine on delay discounting of pair-housed Lewis (LEW) and Fischer 344 (F344) rats. During experiment 2, we examined the sensitivity of nicotine’s effects on delay discounting to pharmacological antagonism of nAChRs or muscarinic AChRs (mAChRs).
Materials and methods
Male LEW and F344 were trained to choose between one food pellet delivered immediately and three food pellets delivered after an increasing delay. During experiment 1, saline and nicotine (0.1–1.0 mg/kg) were tested acutely. During experiment 2, mecamylamine (0.25–1.0 mg/kg) or a nonselective mAChR antagonist, scopolamine (0.01–0.056 mg/kg), was administered prior to nicotine administration.
Nicotine dose dependently reduced delay discounting for both rat strains, and no strain differences were observed (ΔAUC = + 107% for 1.0 mg/kg and + 69.6% for 0.3 mg/kg relative to saline). At some doses, pretreatment with mecamylamine (range ΔAUC = − 27.6 to − 7.3%) or scopolamine (range ΔAUC = − 0.74 to − 51.6%) significantly attenuated the nicotine-induced reduction in some measures of delay discounting for both strains.
Results from experiment 1 suggest that when LEW and F344 are pair housed, there are no strain differences in delay discounting in response to nicotine. Results from experiment 2 suggest that attenuation of nicotine’s effects on delay discounting may not be specific to nAChR antagonism.
KeywordsScopolamine Delay discounting Nicotine Mecamylamine
The authors thank Marissa Turturici, Matthew Eckard, Devin Galdieri, Joshua Tost, Marissa Hovey, and Christopher Iames for their diligent efforts with data collection.
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