Advertisement

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

  • Asti JacksonEmail author
  • Y. Alkhlaif
  • R. L. Papke
  • D. H. Brunzell
  • M. I. Damaj
Original Investigation

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.

Keywords

Nicotine Mice Conditioned place preference Reward 

Notes

Funding

This study was supported by NIH grant [DA 005274 and DA032246] to MID. AJ was supported by T32 (DA007027) from NIH. RLP was supported by [GM57481].

Compliance with ethical standards

Experiments were performed during the light cycle and were approved by the Institutional Animal Care and Use Committee of Virginia Commonwealth University and followed the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Briggs CA, Grønlien JH, Curzon P, Timmermann DB, Ween H, Thorin-Hagene K, Kerr P, Anderson DJ, Malysz J, Dyhring T, Olsen GM, Peters D, Bunnelle WH, Gopalakrishnan M (2009) Role of channel activation in cognitive enhancement mediated by Alpha7 nicotinic acetylcholine receptors. Br J Pharmacol 158:1486–1494.  https://doi.org/10.1111/j.1476-5381.2009.00426.x CrossRefGoogle Scholar
  2. Brioni JD, Kim DJ, O’Neill AB (1996) Nicotine cue: lack of effect of the alpha 7 nicotinic receptor antagonist methyllycaconitine. Eur J Pharmacol 301:1–5.  https://doi.org/10.1016/0014-2999(96)00010-6 CrossRefGoogle Scholar
  3. Brunzell DH, McIntosh JM (2012) Alpha7 nicotinic acetylcholine receptors modulate motivation to self-administer nicotine: implications for smoking and schizophrenia. Neuropsychopharmacology 37:1134–1143.  https://doi.org/10.1038/npp.2011.299 CrossRefGoogle Scholar
  4. de Moura FB, McMahon LR (2017) The contribution of α4β2 and non-α4β2 nicotinic acetylcholine receptors to the discriminative stimulus effects of nicotine and varenicline in mice. Psychopharmacology 234:781–792.  https://doi.org/10.1007/s00213-016-4514-4 CrossRefGoogle Scholar
  5. Freitas K, Carroll FI, Damaj MI (2013a) The antinociceptive effects of nicotinic receptors α7-positive allosteric modulators in murine acute and tonic pain models. J Pharmacol Exp Ther 344:264–275.  https://doi.org/10.1124/jpet.112.197871 CrossRefGoogle Scholar
  6. Freitas K, Ghosh S, Carroll FI, Lichtman AH, Damaj MI (2013b) Effects of alpha 7 positive allosteric modulators in murine inflammatory and chronic neuropathic pain models. Neuropharmacology 65:156–164.  https://doi.org/10.1016/j.neuropharm.2012.08.022 CrossRefGoogle Scholar
  7. Freitas K, Negus S, Carroll FI, Damaj MI (2013c) In vivo pharmacological interactions between a type II positive allosteric modulator of α7 nicotinic ACh receptors and nicotinic agonists in a murine tonic pain model. Br J Pharmacol 169:567–579.  https://doi.org/10.1111/j.1476-5381.2012.02226.x CrossRefGoogle Scholar
  8. Gee, K.W., Olincy, A., Kanner, R., Johnson, L., Hogenkamp, D., Harris, J., Tran, M., Edmonds, S.A., Sauer, W., Yoshimura, R., Johnstone, T., Freedman, R., 2017. First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288 1–8. doi: https://doi.org/10.1177/0269881117691590
  9. Gronlien JH, Hakerud M, Ween H, Thorin-Hagene K, Briggs CA, Gopalakrishnan M, Malysz J (2007) Distinct profiles of 7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes. Mol Pharmacol 72:715–724.  https://doi.org/10.1124/mol.107.035410 CrossRefGoogle Scholar
  10. Grottick AJ, Trube G, Corrigall WA, Huwyler J, Malherbe P, Wyler R, Higgins GA (2000) Evidence that nicotinic α7 receptors are not involved in the hyperlocomotor and rewarding effects of nicotine. J. Pharmacol. Exp. Ther. 294, 1112–1119.Google Scholar
  11. Gurley DA, Lanthorn TH (1998) Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors expressed in Xenopus oocytes. Neurosci Lett 247:107–110.  https://doi.org/10.1016/S0304-3940(98)00306-1 CrossRefGoogle Scholar
  12. Harenza JL, Muldoon PP, De Biasi M, Damaj MI, Miles MF (2014) Genetic variation within the Chrna7 gene modulates nicotine reward-like phenotypes in mice. Genes Brain Behav 13:213–225.  https://doi.org/10.1111/gbb.12113 CrossRefGoogle Scholar
  13. Harvey AL (1995) The pharmacology of galanthamine and its analogues. Pharmacol Ther 68:113–128.  https://doi.org/10.1016/0163-7258(95)02002-0 CrossRefGoogle Scholar
  14. Hopkins TJ, Rupprecht LE, Hayes MR, Blendy JA, Schmidt HD (2012) Galantamine, an acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, attenuates nicotine taking and seeking in rats. Neuropsychopharmacology 37:2310–2321.  https://doi.org/10.1038/npp.2012.83 CrossRefGoogle Scholar
  15. Jackson, A., Bagdas, D., Muldoon, P.P., Lichtman, A.H., Carroll, F.I., Greenwald, M., Miles, M.F., Damaj, M.I., 2017. In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: implication for nicotine dependence. Neuropharmacology 118. doi: https://doi.org/10.1016/j.neuropharm.2017.03.005
  16. Jackson A, Papke RL, Damaj MI (2018) Pharmacological modulation of the α7 nicotinic acetylcholine receptor in a mouse model of mecamylamine-precipitated nicotine withdrawal. Psychopharmacology 235:1897–1905.  https://doi.org/10.1007/s00213-018-4879-7 CrossRefGoogle Scholar
  17. Kota D, Martin BR, Robinson SE, Damaj MI (2007) Nicotine dependence and reward differ between adolescent and adult male mice. J Pharmacol Exp Ther 322:399–407.  https://doi.org/10.1124/jpet.107.121616 CrossRefGoogle Scholar
  18. Livingstone PD, Srinivasan J, Kew JNC, Dawson LA, Gotti C, Moretti M, Shoaib M, Wonnacott S (2009) alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex. Eur J Neurosci 29:539–550.  https://doi.org/10.1111/j.1460-9568.2009.06613.x CrossRefGoogle Scholar
  19. Maelicke A, Albuquerque EX (2000) Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer’s disease. Eur J Pharmacol 393:165–170.  https://doi.org/10.1177/0095327X0403100111 CrossRefGoogle Scholar
  20. Kowal NM, Ahring PK, Liao VWY, Indurti DC, Harvey BS, O'Connor SM, Chebib M, Olafsdottir ES, Balle T, (2017) Galantamine is not a positive allosteric modulator of human α4β2 or α7 nicotinic acetylcholine receptors. British Journal of Pharmacology 175 (14):2911–2925.Google Scholar
  21. Papke RL, Chojnacka K, Horenstein NA (2014) The minimal pharmacophore for silent agonism of the α7 nicotinic acetylcholine receptor. J Pharmacol Exp Ther 350:665–680.  https://doi.org/10.1124/jpet.114.215236 CrossRefGoogle Scholar
  22. Papke RL, Bagdas D, Kulkarni AR, Gould T, Alsharari SD, Thakur GA, Damaj MI (2015) The analgesic-like properties of the alpha7 nAChR silent agonist NS6740 is associated with non-conducting conformations of the receptor. Neuropharmacology 0:34–42.  https://doi.org/10.1016/j.neuropharm.2014.12.002 CrossRefGoogle Scholar
  23. Papke R, Stokes C, Damaj M, Thakur G, Manther K, Treinin M, Bagdas D, Kulkarni AR, Horenstein NA (2017) Persistent activation of α 7 nicotinic ACh receptors associated with stable induction of different desensitized states. Br J Pharmacol 1–17:1838–1854.  https://doi.org/10.1111/bph.13851 Google Scholar
  24. Papke RL, Peng C, Kumar A, Stokes C (2018) NS6740, an α7 nicotinic acetylcholine receptor silent agonist, disrupts hippocampal synaptic plasticity. Neurosci Lett 677:6–13.  https://doi.org/10.1586/14737175.2015.1028369.Focused CrossRefGoogle Scholar
  25. Perkins KA, Roy Chengappa KN, Karelitz JL, Boldry MC, Michael V, Herb T, Gannon J, Brar J, Ford L, Rassnick S, Brunzell DH (2018) Initial cross-over test of a positive allosteric modulator of Alpha-7 nicotinic receptors to aid cessation in smokers with or without schizophrenia. Neuropsychopharmacology 43:1334–1342.  https://doi.org/10.1038/npp.2017.292 CrossRefGoogle Scholar
  26. Pieschl RL, Miller R, Jones KM, Post-Munson DJ, Chen P, Newberry K, Benitex Y, Molski T, Morgan D, McDonald IM, Macor JE, Olson RE, Asaka Y, Digavalli S, Easton A, Herrington J, Westphal RS, Lodge NJ, Zaczek R, Bristow LJ, Li YW (2017) Effects of BMS-902483, an α7 nicotinic acetylcholine receptor partial agonist, on cognition and sensory gating in relation to receptor occupancy in rodents. Eur J Pharmacol 807:1–11.  https://doi.org/10.1016/j.ejphar.2017.04.024 CrossRefGoogle Scholar
  27. Quadri M, Papke RL, Horenstein NA (2016) Dissection of N,N-diethyl-N′-phenylpiperazines as α7 nicotinic receptor silent agonists. Bioorg Med Chem 24:286–293.  https://doi.org/10.1016/j.bmc.2015.12.017 CrossRefGoogle Scholar
  28. Samochocki M (2003) Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors. J Pharmacol Exp Ther 305:1024–1036.  https://doi.org/10.1124/jpet.102.045773 CrossRefGoogle Scholar
  29. Schilström B, Nomikos GG, Nisell M, Hertel P, Svensson TH (1998) N-methyl-D-aspartate receptor antagonism in the ventral tegmental area diminishes the systemic nicotine-induced dopamine release in the nucleus accumbens. Neuroscience 82:781–789.  https://doi.org/10.1016/S0306-4522(97)00243-1 CrossRefGoogle Scholar
  30. Séguéla P, Wadiche J, Dineley-Miller K, Dani JA, Patrick JW (1993) Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium. J Neurosci 13:596–604CrossRefGoogle Scholar
  31. Thomsen MS, Mikkelsen JD (2012) Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of α7 nicotinic acetylcholine receptors. J Neurochem 123:73–83.  https://doi.org/10.1111/j.1471-4159.2012.07876.x CrossRefGoogle Scholar
  32. Timmermann DB, Grønlien JH, Kohlhaas KL, Nielsen EØ, Dam E, Jørgensen TD, Ahring PK, Peters D, Holst D, Chrsitensen JK, Malysz J, Briggs CA, Gopalakrishnan M, Olsen GM (2007) An allosteric modulator of the α7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther 323:294–307.  https://doi.org/10.1124/jpet.107.120436.vidual CrossRefGoogle Scholar
  33. Vicens P, Ribes D, Heredia L, Torrente M, Domingo JL (2013) Motor and anxiety effects of PNU-282987, an alpha7 nicotinic receptor agonist, and stress in an animal model of Alzheimer’s disease. Curr Alzheimer Res 10:516–523.  https://doi.org/10.2174/15672050113109990130 CrossRefGoogle Scholar
  34. Wang J, Papke RL, Stokes C, Horenstein NA (2012) Potential state-selective hydrogen bond formation can modulate activation and desensitization of the ␣ 7 nicotinic acetylcholine receptor * □. J Biol Chem 287:21957–21969.  https://doi.org/10.1074/jbc.M112.339796 CrossRefGoogle Scholar
  35. Williams DK, Stokes C, Horenstein NA, Papke RL (2011a) The effective opening of nicotinic acetylcholine receptors with single agonist binding sites. J Gen Physiol 137:369–384.  https://doi.org/10.1085/jgp.201010587 CrossRefGoogle Scholar
  36. Williams DK, Wang J, Papke RL (2011b) Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations. Biochem Pharmacol 82:915–930.  https://doi.org/10.1016/j.bcp.2011.05.001 CrossRefGoogle Scholar
  37. Winterer G, Gallinat J, Brinkmeyer J, Musso F, Kornhuber J, Thuerauf N, Rujescu D, Favis R, Sun Y, Franc MA, Ouwerkerk-Mahadevan S, Janssens L, Timmers M, Streffer JR (2013) Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology 64:197–204.  https://doi.org/10.1016/j.neuropharm.2012.06.040 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Asti Jackson
    • 1
    Email author
  • Y. Alkhlaif
    • 2
  • R. L. Papke
    • 3
  • D. H. Brunzell
    • 2
  • M. I. Damaj
    • 2
  1. 1.Department of PsychiatryYale School of MedicineNew HavenUSA
  2. 2.Department of Pharmacology and Toxicology, School of MedicineVirginia Commonwealth UniversityRichmondUSA
  3. 3.Department of Pharmacology and TherapeuticsUniversity of FloridaGainesvilleUSA

Personalised recommendations