Abstract
Rationale
Tobacco use is implicated in approximately 440,000 deaths per year, making it the leading cause of preventable death in the United States. Although it is generally recognized that tobacco use is correlated with a variety of health-related complications, many smokers are unsuccessful in their efforts to stop smoking using current cessation therapies.
Objectives
Given that nicotine is the addictive component of tobacco, successful smoking cessation therapies must address the various processes, including reward, which contribute to nicotine addiction. As such, determining the nicotinic receptor subtypes involved in nicotine reward is of utmost importance to understanding how nicotine addiction progresses.
Methods
Conditioned place preference (CPP) in three-chamber conditioning boxes was performed. For antagonist studies, drug was given on all conditioning sessions 10 min before nicotine or saline injection and placement in the boxes.
Results
We have demonstrated that a pretreatment with the α4β2 subunit of the nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine (2.0 mg/kg, s.c.) blocked nicotine (0.5 mg/kg, s.c.) CPP in wild-type mice (C57BL/6 mice). In contrast, pretreatment with an antagonist of the α7 subunit of the nAChR, methyllycaconitine (MLA, 5.0 or 10.0 mg/kg, s.c.), had no effect on this behavior. Finally, we showed that mice lacking the β2 subunit of the nAChR did not exhibit nicotine CPP while α7 knock-out mice did.
Conclusion
Taken together, these data suggest that the β2 subunit of the nAChR is critically involved in nicotine reward as measured by CPP.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- nAChR:
-
nicotinic acetylcholine receptor
- CPP:
-
conditioned place preference
- DHβE:
-
dihydro-β-erythroidine
- MLA:
-
methyllycaconitine
References
Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl) 153:31–43
Caldarone BJ, Duman CH, Picciotto MR (2000) Fear conditioning and latent inhibition in mice lacking the high affinity subclass of nicotinic acetylcholine receptors in the brain. Neuropharmacology 39:2779–2784
Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. Oxford University Press
Corrigall WA, Coen KM, Adamson KL (1994) Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res 653:278–284
Couturier S, Bertrand D, Matter JM, Hernandez MC, Bertrand S, Millar N, Valera S, Barkas T, Ballivet M (1990) A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX. Neuron 5:847–856
Damaj MI, Welch SP, Martin BR (1995) In vivo pharmacological effects of dihydro-beta-erythroidine, a nicotinic antagonist, in mice. Psychopharmacology (Berl) 117:67–73
Damaj MI, Glassco W, Dukat M, Martin BR (1999) Pharmacological characterization of nicotine-induced seizures in mice. J Pharmacol Exp Ther 291:1284–1291
Damaj MI, Kao W, Martin BR (2003) Characterization of spontaneous and precipitated nicotine withdrawal in the mouse. J Pharmacol Exp Ther 307:526–534
Di Chiara G, Imperato A (1979) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278
Fudala PJ, Teoh KW, Iwamoto ET (1985) Pharmacologic characterization of nicotine-induced conditioned place preference. Pharmacol Biochem Behav 22:237–241
Grady S, Marks MJ, Wonnacott S, Collins AC (1992) Characterization of nicotinic receptor-mediated [3H]dopamine release from synaptosomes prepared from mouse striatum. J Neurochem 59:848–856
Grottick AJ, Trube G, Corrigall WA, Huwyler J, Malherbe P, Wyler R, Higgins GA (2000) Evidence that nicotinic alpha(7) receptors are not involved in the hyperlocomotor and rewarding effects of nicotine. J Pharmacol Exp Ther 294:1112–1119
Harvey SC, Maddox FN, Luetje CW (1996) Multiple determinants of dihydro-beta-erythroidine sensitivity on rat neuronal nicotinic receptor alpha subunits. J Neurochem 67:1953–1959
Khiroug SS, Khiroug L, Yakel JL (2004) Rat nicotinic acetylcholine receptor alpha2beta2 channels: comparison of functional properties with alpha4beta2 channels in Xenopus oocytes. Neuroscience 124:817–822
Klink R, de Kerchove d’Exaerde A, Zoli M, Changeux JP (2001) Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci 21:1452–1463
Laviolette SR, van der Kooy D (2003) Blockade of mesolimbic dopamine transmission dramatically increases sensitivity to the rewarding effects of nicotine in the ventral tegmental area. Mol Psychiatry 8:50–99
Laviolette SR, Alexson TO, van der Kooy D (2002) Lesions of the tegmental pedunculopontine nucleus block the rewarding effects and reveal the aversive effects of nicotine in the ventral tegmental area. J Neurosci 22:8653–8660
Mansvelder HD, McGehee DS (2000) Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27:349–357
Markou A, Paterson NE (2001) The nicotinic antagonist methyllycaconitine has differential effects on nicotine self-administration and nicotine withdrawal in the rat. Nicotine Tob Res 3:361–373
Maskos U, Molles BE, Pons S, Besson M, Guiard BP, Guilloux JP, Evrard A, Cazala P, Cormier A, Mameli-Engvall M, Dufour N, Cloez-Tayarani I, Bemelmans AP, Mallet J, Gardier AM, David V, Faure P, Granon S, Changeux JP (2005) Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature 436:103–107
Orr-Urtreger A, Goldner FM, Saeki M, Lorenzo I, Goldberg L, De Biasi M, Dani JA, Patrick JW, Beaudet AL (1997) Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci 17:9165–9171
Picciotto MR, Zoli M, Lena C, Bessis A, Lallemand Y, Le Novere N, Vincent P, Pich EM, Brulet P, Changeux JP (1995) Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature 374:65–67
Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM, Fuxe K, Changeux JP (1998) Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391:173–177
Turek JW, Kang CH, Campbell JE, Arneric SP, Sullivan JP (1995) A sensitive technique for the detection of the alpha 7 neuronal nicotinic acetylcholine receptor antagonist, methyllycaconitine, in rat plasma and brain. J Neurosci Methods 61:113–118
Vaszar LT, Sarinas PS, Lillington GA (2002) Achieving tobacco cessation: current status, current problems, future possibilities. Respiration 69:381–384
Watkins SS, Epping-Jordan MP, Koob GF, Markou A (1999) Blockade of nicotine self-administration with nicotinic antagonists in rats. Pharmacol Biochem Behav 62:743–751
Williams M, Robinson JL (1984) Binding of the nicotinic cholinergic antagonist, dihydro-beta-erythroidine, to rat brain tissue. J Neurosci 4:2906–2911
Zachariou V, Caldarone BJ, Weathers-Lowin A, George TP, Elsworth JD, Roth RH, Changeux JP, Picciotto MR (2001) Nicotine receptor inactivation decreases sensitivity to cocaine. Neuropsychopharmacology 24:576–589
Zoli M, Picciotto MR, Ferrari R, Cocchi D, Changeux JP (1999) Increased neurodegeneration during ageing in mice lacking high-affinity nicotine receptors. EMBO J 18:1235–1244
Acknowledgements
This research was generously supported by NIH DA-05274, DA-12610, and DA-07027.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Walters, C.L., Brown, S., Changeux, JP. et al. The β2 but not α7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice. Psychopharmacology 184, 339–344 (2006). https://doi.org/10.1007/s00213-005-0295-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-005-0295-x