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.
The stipend for author JEO was provided by NIGMS T32 GM081741, and this research was supported in part by the Master’s Thesis Grant (Basic Research) from the Society for the Advancement of Behavior Analysis, as well as funding from the West Virginia University Department of Psychology.
- Barlow P, McKee M, Reeves A, Galea G, Stuckler D (2016) Time-discounting and tobacco smoking: a systematic review and network analysis. Int J Epidemiol. https://doi.org/10.1093/ije/dyw233
- Benowitz NL (2009) Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 49:57–71. https://doi.org/10.1146/annurev.pharmtox.48.113006.094742 CrossRefPubMedPubMedCentralGoogle Scholar
- Huskinson SL, Krebs CA, Anderson KG (2012) Strain differences in delay discounting between Lewis and Fischer 344 rats as baseline and following acute and chronic administration of d-amphetamine. Pharmacol Biochem Behav 101:403–416. https://doi.org/10.1016/j.pbb.2012.02.005 CrossRefPubMedPubMedCentralGoogle Scholar
- Mazur JE (1987) An adjusting amount procedure for studying delayed reinforcement. In: Commons ML, Mazur JE, Nevin JA, Rachlin H (eds) Quantitative analysis of behavior: the effects of delay and of intervening events on reinforcement value. Erlbaum, Hillsdale, pp 55–73Google Scholar
- Mendez IA, Gilbert RJ, Bizon JL, Setlow B (2012) Effects of acute administration of nicotinic and muscarinic cholinergic agonists and antagonists on performance in different cost-benefit decision making tasks in rats. Psychopharmacology 224:489–499. https://doi.org/10.1007/s00213-012-2777-y CrossRefPubMedPubMedCentralGoogle Scholar
- U.S. Department of Health and Human Services (2014) The health consequences of smoking—50 years of progress: a report of the Surgeon General. Altanta, GA: U.S. Department of Health and Human Services, Center for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and HealthGoogle Scholar
- Winstanley CA, Theobald DE, Dalley JW, Cardinal RN, Robbins TW (2006) Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice. Cereb Cortex 16:106–114. https://doi.org/10.1093/cercor/bhi088 CrossRefPubMedGoogle Scholar
- Xie X, Arguello AA, Reittinger AM, Wells AM, Fuchs RA (2012) Role of nicotinic acetylcholine receptors in the effects of cocaine-paired contextual stimuli on impulsive decision making in rats. Psychopharmacology 223:271–279. https://doi.org/10.1007/s00213-012-2715-z CrossRefPubMedPubMedCentralGoogle Scholar