Donepezil, an Acetylcholinesterase Inhibitor, Attenuates Nicotine Self-administration and Reinstatement of Nicotine Seeking in Rats

Overview

Journal Addict Biol

Specialty Psychiatry

Date 2012 Dec 13

PMID 23231479

Citations 16

Authors

Blake A Kimmey

Laura E Rupprecht

Matthew R Hayes

Heath D Schmidt

Affiliations

Soon will be listed here.

Abstract

Nicotine craving and cognitive impairments represent core symptoms of nicotine withdrawal and predict relapse in abstinent smokers. Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Donepezil is an acetylcholinesterase inhibitor that has been shown previously to improve cognition in healthy non-treatment-seeking smokers. However, there are no studies examining the effects of donepezil on nicotine self-administration and/or the reinstatement of nicotine-seeking behavior in rodents. The present experiments were designed to determine the effects of acute donepezil administration on nicotine taking and the reinstatement of nicotine-seeking behavior, an animal model of relapse in abstinent human smokers. Moreover, the effects of acute donepezil administration on sucrose self-administration and sucrose seeking were also investigated in order to determine whether donepezil's effects generalized to other reinforced behaviors. Acute donepezil administration (1.0 or 3.0 mg/kg, i.p.) attenuated nicotine, but not sucrose self-administration maintained on a fixed-ratio 5 schedule of reinforcement. Donepezil administration also dose-dependently attenuated the reinstatement of both nicotine- and sucrose-seeking behaviors. Commonly reported adverse effects of donepezil treatment in humans are nausea and vomiting. However, at doses required to attenuate nicotine self-administration in rodents, no effects of donepezil on nausea/malaise as measured by pica were observed. Collectively, these results indicate that increased extracellular acetylcholine levels are sufficient to attenuate nicotine taking and seeking in rats and that these effects are not due to adverse malaise symptoms such as nausea.

Citing Articles

Paternal preconception donepezil exposure enhances learning in offspring.

Fan G, Pan T, Ji X, Jiang C, Wang F, Liu X Behav Brain Funct. 2024; 20(1):25.

PMID: 39342229 PMC: 11439325. DOI: 10.1186/s12993-024-00252-z.

Targeting GLP-1 receptors to reduce nicotine use disorder: Preclinical and clinical evidence.

Herman R, Schmidt H Physiol Behav. 2024; 281:114565.

PMID: 38663460 PMC: 11128349. DOI: 10.1016/j.physbeh.2024.114565.

PYY infused systemically or directly into the VTA attenuates fentanyl seeking in male rats.

Caffrey A, Lavecchia E, Merkel R, Zhang Y, Chichura K, Hayes M Neuropharmacology. 2023; 239:109686.

PMID: 37572954 PMC: 10528880. DOI: 10.1016/j.neuropharm.2023.109686.

Liraglutide attenuates nicotine self-administration as well as nicotine seeking and hyperphagia during withdrawal in male and female rats.

Herman R, Hayes M, Audrain-McGovern J, Ashare R, Schmidt H Psychopharmacology (Berl). 2023; 240(6):1373-1386.

PMID: 37129617 PMC: 11088902. DOI: 10.1007/s00213-023-06376-w.

Vitamin D3 reduces hippocampal NR2A and anxiety in nicotine withdrawal mice.

Wu B, Tao X, Liu C, Li H, Jiang T, Chen Z Transl Neurosci. 2021; 12(1):273-281.

PMID: 34178387 PMC: 8200643. DOI: 10.1515/tnsci-2020-0166.

References

Kelly D, McMahon R, Weiner E, Boggs D, Dickinson D, Conley R . Lack of beneficial galantamine effect for smoking behavior: a double-blind randomized trial in people with schizophrenia. Schizophr Res. 2008; 103(1-3):161-8. PMC: 2547986. DOI: 10.1016/j.schres.2008.04.027. View

Taylor Jr D, Hasselblad V, Henley S, Thun M, Sloan F . Benefits of smoking cessation for longevity. Am J Public Health. 2002; 92(6):990-6. PMC: 1447499. DOI: 10.2105/ajph.92.6.990. View

Giarola A, Auber A, Chiamulera C . Acetylcholinesterase inhibitors partially generalize to nicotine discriminative stimulus effect in rats. Behav Pharmacol. 2010; 22(1):1-6. DOI: 10.1097/FBP.0b013e328341e9dd. View

Schmidt H, Anderson S, Famous K, Kumaresan V, Pierce R . Anatomy and pharmacology of cocaine priming-induced reinstatement of drug seeking. Eur J Pharmacol. 2005; 526(1-3):65-76. DOI: 10.1016/j.ejphar.2005.09.068. View

Matta S, Balfour D, Benowitz N, Boyd R, Buccafusco J, Caggiula A . Guidelines on nicotine dose selection for in vivo research. Psychopharmacology (Berl). 2006; 190(3):269-319. DOI: 10.1007/s00213-006-0441-0. View

Yan Y, Pushparaj A, Le Strat Y, Gamaleddin I, Barnes C, Justinova Z . Blockade of dopamine d4 receptors attenuates reinstatement of extinguished nicotine-seeking behavior in rats. Neuropsychopharmacology. 2011; 37(3):685-96. PMC: 3260983. DOI: 10.1038/npp.2011.245. View

Grasing K, He S, Yang Y . Dose-related effects of the acetylcholinesterase inhibitor tacrine on cocaine and food self-administration in rats. Psychopharmacology (Berl). 2007; 196(1):133-42. DOI: 10.1007/s00213-007-0944-3. View

Hiranita T, Nawata Y, Sakimura K, Anggadiredja K, Yamamoto T . Suppression of methamphetamine-seeking behavior by nicotinic agonists. Proc Natl Acad Sci U S A. 2006; 103(22):8523-7. PMC: 1482524. DOI: 10.1073/pnas.0600347103. View

Shalev U, Grimm J, Shaham Y . Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev. 2002; 54(1):1-42. DOI: 10.1124/pr.54.1.1. View

10.

Hopkins T, Rupprecht L, Hayes M, Blendy J, Schmidt H . Galantamine, an acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, attenuates nicotine taking and seeking in rats. Neuropsychopharmacology. 2012; 37(10):2310-21. PMC: 3422495. DOI: 10.1038/npp.2012.83. View

11.

George O, Lloyd A, Carroll F, Damaj M, Koob G . Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration. Psychopharmacology (Berl). 2010; 213(4):715-22. PMC: 3033995. DOI: 10.1007/s00213-010-2024-3. View

12.

Kenny P, Markou A . Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav. 2002; 70(4):531-49. DOI: 10.1016/s0091-3057(01)00651-7. View

13.

Fowler C, Lu Q, Johnson P, Marks M, Kenny P . Habenular α5 nicotinic receptor subunit signalling controls nicotine intake. Nature. 2011; 471(7340):597-601. PMC: 3079537. DOI: 10.1038/nature09797. View

14.

Liu Y, Malik N, Sanger G, Friedman M, Andrews P . Pica--a model of nausea? Species differences in response to cisplatin. Physiol Behav. 2005; 85(3):271-7. DOI: 10.1016/j.physbeh.2005.04.009. View

15.

Diehl A, Nakovics H, Croissant B, Smolka M, Batra A, Mann K . Galantamine reduces smoking in alcohol-dependent patients: a randomized, placebo-controlled trial. Int J Clin Pharmacol Ther. 2006; 44(12):614-22. DOI: 10.5414/cpp44614. View

16.

Liang Y, Tang X . Comparative effects of huperzine A, donepezil and rivastigmine on cortical acetylcholine level and acetylcholinesterase activity in rats. Neurosci Lett. 2004; 361(1-3):56-9. DOI: 10.1016/j.neulet.2003.12.071. View

17.

Kanoski S, Rupprecht L, Fortin S, De Jonghe B, Hayes M . The role of nausea in food intake and body weight suppression by peripheral GLP-1 receptor agonists, exendin-4 and liraglutide. Neuropharmacology. 2012; 62(5-6):1916-27. PMC: 4183930. DOI: 10.1016/j.neuropharm.2011.12.022. View

18.

Kosasa T, Kuriya Y, Matsui K, Yamanishi Y . Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. Eur J Pharmacol. 1999; 380(2-3):101-7. DOI: 10.1016/s0014-2999(99)00545-2. View

19.

Hughes J, Hatsukami D . Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986; 43(3):289-94. DOI: 10.1001/archpsyc.1986.01800030107013. View

20.

Tuesta L, Fowler C, Kenny P . Recent advances in understanding nicotinic receptor signaling mechanisms that regulate drug self-administration behavior. Biochem Pharmacol. 2011; 82(8):984-95. PMC: 3163076. DOI: 10.1016/j.bcp.2011.06.026. View