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α7 Nicotinic acetylcholine receptors in the central amygdaloid nucleus alter naloxone-induced withdrawal following a single exposure to morphine

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Abstract

Rationale

Negative motivational withdrawal from acute opiate dependence was induced by an opioid antagonist, and the withdrawal signs prevented by pretreatment with nicotine.

Objectives

The present study was undertaken to examine the mechanism of nicotine-induced attenuation of withdrawal precipitated by naloxone in rats administered a single dose of morphine.

Methods

Conditioned place aversion (CPA) was precipitated by naloxone in rats exposed once to morphine. Nicotinic acetylcholine receptor (nAChR) agonists were microinjected into the central amygdaloid nucleus (CeA) before naloxone was administered. Additionally, c-Fos expression in the amygdala was measured in rats exposed to α7 nAChR ligands.

Results

The microinjection of nicotine (0.3 and 1.0 μg/μl) into the CeA dose-dependently inhibited naloxone-induced CPA. This inhibition of CPA was reversed by methyllycaconitine (MLA), an α7 nAChR antagonist. CPA was also significantly attenuated by the microinjection of tropisetron (3.0 μg/μl), an α7 nAChR agonist and 5-hydroxytriptamine 3 (5-HT3) receptor antagonist, but not by ondansetron (1.0 and 3.0 μg/μl), a 5-HT3 receptor antagonist. The microinjection of PNU-282987 (3.0 μg/μl), a selective α7 nAChR agonist, into the CeA also inhibited CPA. Furthermore, nicotine increased c-Fos expression in the CeA, but not the medial or basolateral amygdaloid nucleus. The increase of c-Fos in the CeA was significantly inhibited by MLA.

Conclusion

Nicotine-induced attenuation of CPA precipitated by naloxone is mediated by the α7 nAChR subtype, and the CeA is one of the regions of the brain involved in the effect of nicotine on acutely opiate-dependent subjects.

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References

  • Araki H, Kawakami KY, Jin C, Suemaru K, Kitamura Y, Nagata M, Futagami K, Shibata K, Kawasaki H, Gomita Y (2004) Nicotine attenuates place aversion induced by naloxone in single-dose, morphine-treated rats. Psychopharmacology 171:398–404

    Article  PubMed  CAS  Google Scholar 

  • Azar MR, Jones BC, Schulteis G (2003) Conditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal. Psychopharmacology 170:42–50

    Article  PubMed  CAS  Google Scholar 

  • Bhatnagar S, Sun LM, Raber J, Maren S, Julius D, Dallman MF (2004) Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor. Physiol Behav 81:545–555

    Article  PubMed  CAS  Google Scholar 

  • Bickel WK, Stitzer ML, Liebson IA, Bigelow GE (1988) Acute physical dependence in man: effects of naloxone after brief morphine exposure. J Pharmacol Exp Ther 244:126–132

    PubMed  CAS  Google Scholar 

  • Bodnar AL, Cortes-Burgos LA, Cook KK, Dinh DM, Groppi VE, Hajos M, Higdon NR, Hoffmann WE, Hurst RS, Myers JK, Rogers BN, Wall TM, Wolfe ML, Wong E (2005) Discovery and structure-activity relationship of quinuclidine benzamides as agonists of alpha7 nicotinic acetylcholine receptors. J Med Chem 48:905–908

    Article  PubMed  CAS  Google Scholar 

  • Carboni E, Acquas E, Leone P, Perezzani L, Di Chiara G (1988) 5-HT3 receptor antagonists block morphine- and nicotine-induced place-preference conditioning. Eur J Pharmacol 22:159–160

    Article  Google Scholar 

  • Chartoff EH, Mague SD, Barhight MF, Smith AM, Carlezon WA Jr (2006) Behavioral and molecular effects of dopamine D1 receptor stimulation during naloxone-precipitated morphine withdrawal. J Neurosci 26:6450–6457

    Article  PubMed  CAS  Google Scholar 

  • Chu LF, Liang DY, Li X, Sahbaie P, D’arcy N, Liao G, Peltz G, David Clark J (2009) From mouse to man: the 5-HT3 receptor modulates physical dependence on opioid narcotics. Pharmacogenet Genomics 19:193–205

    Article  PubMed  CAS  Google Scholar 

  • Cui R, Suemaru K, Li B, Kohnomi S, Araki H (2009) Tropisetron attenuates naloxone-induced place aversion in single-dose morphine-treated rats: role of alpha7 nicotinic receptors. Eur J Pharmacol 609:74–77

    Article  PubMed  CAS  Google Scholar 

  • Davis M, Rainnie D, Cassell M (1994) Neurotransmission in the rat amygdala related to fear and anxiety. Trends Neurosci 17:208–214

    Article  PubMed  CAS  Google Scholar 

  • Easterling KW, Holtzman SG (1997) Intracranial self-stimulation in rats: sensitization to an opioid antagonist following acute or chronic treatment with mu opioid agonists. J Pharmacol Exp Ther 281:188–199

    PubMed  CAS  Google Scholar 

  • Frenois F, Cador M, Caillé S, Stinus L, Le Moine C (2002) Neural correlates of the motivational and somatic components of naloxone-precipitated morphine withdrawal. Eur J Neurosci 16:1377–1389

    Article  PubMed  Google Scholar 

  • Georges F, Stinus L, Bloch B, Le Moine C (1999) Chronic morphine exposure and spontaneous withdrawal are associated with modifications of dopamine receptor and neuropeptide gene expression in the rat striatum. Eur J Neurosci 11:481–490

    Article  PubMed  CAS  Google Scholar 

  • Gracy KN, Dankiewicz LA, Koob GF (2001) Opiate withdrawal-induced fos immunoreactivity in the rat extended amygdala parallels the development of conditioned place aversion. Neuropsychopharmacology 24:152–160

    Article  PubMed  CAS  Google Scholar 

  • Haertzen CA, Hooks NT Jr (1969) Changes in personality and subjective experience associated with the chronic administration and withdrawal of opiates. J Nerv Ment Dis 148:606–614

    Article  PubMed  CAS  Google Scholar 

  • Han ZY, Zoli M, Cardona A, Bourgeois JP, Changeux JP, Le Novère N (2003) Localization of [3H]nicotine, [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin binding sites in the brain of Macaca mulatta. J Comp Neurol 461:49–60

    Article  PubMed  CAS  Google Scholar 

  • Higgins GA, Nguyen P, Joharchi N, Sellers EM (1991) Effects of 5-HT3 receptor antagonists on behavioural measures of naloxone-precipitated opioid withdrawal. Psychopharmacology 105:322–328

    Article  PubMed  CAS  Google Scholar 

  • Jin C, Araki H, Nagata M, Suemaru K, Shibata K, Kawasaki H, Hamamura T, Gomita Y (2004) Withdrawal-induced c-Fos expression in the rat centromedial amygdala 24 h following a single morphine exposure. Psychopharmacology 175:428–435

    PubMed  CAS  Google Scholar 

  • Jin C, Araki H, Nagata M, Shimosaka R, Shibata K, Suemaru K, Kawasaki H, Gomita Y (2005) Expression of c-Fos in the rat central amygdala accompanies the acquisition but not expression of conditioned place aversion induced by withdrawal from acute morphine dependence. Behav Brain Res 161:107–112

    Article  PubMed  CAS  Google Scholar 

  • Kankaanpää A, Meririnne E, Seppälä T (2002) 5-HT3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not methylphenidate-induced neurochemical and behavioral effects in the rat. Psychopharmacology 159:341–350

    Article  PubMed  Google Scholar 

  • Kelsey JE, Arnold SR (1994) Lesions of the dorsomedial amygdala, but not the nucleus accumbens, reduce the aversiveness of morphine withdrawal in rats. Behav Neurosci 108:1119–1127

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (1999) The role of the striatopallidal and extended amygdala systems in drug addiction. Ann N Y Acad Sci 877:445–460

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, Le Moal M (2005) Neurobiology of addiction. Academic, San Diego

    Google Scholar 

  • Liu J, Schulteis G (2004) Brain reward deficits accompany naloxone-precipitated withdrawal from acute opioid dependence. Pharmacol Biochem Behav 79:101–108

    Article  PubMed  CAS  Google Scholar 

  • Loughlin SE, Islas MI, Cheng MY, Lee AG, Villegier AS, Leslie FM (2006) Nicotine modulation of stress-related peptide neurons. J Comp Neurol 497:575–588

    Article  PubMed  CAS  Google Scholar 

  • Macor JE, Gurley D, Lanthorn T, Loch J, Mack RA, Mullen G, Tran O, Wright N, Gordon JC (2001) The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist. Bioorg Med Chem Lett 11:319–321

    Article  PubMed  CAS  Google Scholar 

  • Martin WR, Eades CG (1964) A comparison between acute and chronic physical dependence in the chronic spinal dog. J Pharmacol Exp Ther 146:385–394

    PubMed  CAS  Google Scholar 

  • Mathieu-Kia AM, Pages C, Besson MJ (1998) Inducibility of c-Fos protein in visuo-motor system and limbic structures after acute and repeated administration of nicotine in the rat. Synapse 29:343–354

    Article  PubMed  CAS  Google Scholar 

  • McDonald RV, Parker LA, Siegel S (1997) Conditioned sucrose aversions produced by naloxone-precipitated withdrawal from acutely administered morphine. Pharmacol Biochem Behav 58:1003–1008

    Article  PubMed  CAS  Google Scholar 

  • Motoshima S, Suemaru K, Kawasaki Y, Jin C, Kawasaki H, Gomita Y, Araki H (2005) Effects of alpha4beta2 and alpha7 nicotinic acetylcholine receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats. Eur J Pharmacol 519:91–95

    Article  PubMed  CAS  Google Scholar 

  • Panagis G, Hildebrand BE, Svensson TH, Nomikos GG (2000) Selective c-fos induction and decreased dopamine release in the central nucleus of amygdala in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Synapse 35:15–25

    Article  PubMed  CAS  Google Scholar 

  • Parker LA, Joshi A (1998) Naloxone-precipitated morphine withdrawal induced place aversions: effect of naloxone at 24 hours postmorphine. Pharmacol Biochem Behav 61:331–333

    Article  PubMed  CAS  Google Scholar 

  • Parker LA, Cyr JA, Santi AN, Burton PD (2002) The aversive properties of acute morphine dependence persist 48 h after a single exposure to morphine: evaluation by taste and place conditioning. Pharmacol Biochem Behav 72:87–92

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Academic, San Diego

    Google Scholar 

  • Rodríguez de Fonseca F, Navarro M (1998) Role of the limbic system in dependence on drugs. Ann Med 30:397–405

    Article  PubMed  Google Scholar 

  • Salminen O, Seppä T, Gäddnäs H, Ahtee L (1999) The effects of acute nicotine on the metabolism of dopamine and the expression of Fos protein in striatal and limbic brain areas of rats during chronic nicotine infusion and its withdrawal. J Neurosci 19:8145–8151

    PubMed  CAS  Google Scholar 

  • Schulteis G, Heyser CJ, Koob GF (1997) Opiate withdrawal signs precipitated by naloxone following a single exposure to morphine: potentiation with a second morphine exposure. Psychopharmacology 129:56–65

    Article  PubMed  CAS  Google Scholar 

  • Schulteis G, Heyser CJ, Koob GF (1999) Differential expression of response-disruptive and somatic indices of opiate withdrawal during the initiation and development of opiate dependence. Behav Pharmacol 10:235–242

    Article  PubMed  CAS  Google Scholar 

  • 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 13:596–604

    PubMed  Google Scholar 

  • Shram MJ, Funk D, Li Z, Lê AD (2007) Acute nicotine enhances c-fos mRNA expression differentially in reward-related substrates of adolescent and adult rat brain. Neurosci Lett 18:286–291

    Article  Google Scholar 

  • Simpson K, Spencer CM, McClellan KJ (2000) Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 59:1297–1315

    Article  PubMed  CAS  Google Scholar 

  • Taraschenko OD, Panchal V, Maisonneuve IM, Glick SD (2005) Is antagonism of alpha3beta4 nicotinic receptors a strategy to reduce morphine dependence? Eur J Pharmacol 513:207–218

    Article  PubMed  CAS  Google Scholar 

  • Veinante P, Stoeckel ME, Lasbennes F, Freund-Mercier MJ (2003) c-Fos and peptide immunoreactivities in the central extended amygdala of morphine-dependent rats after naloxone-precipitated withdrawal. Eur J Neurosci 18:1295–1305

    Article  PubMed  Google Scholar 

  • Watanabe T, Nakagawa T, Yamamoto R, Maeda A, Minami M, Satoh M (2002) Involvement of glutamate receptors within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats. Jpn J Pharmacol 88:399–406

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by a grant from the Smoking Research Foundation of Japan.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Shigeru Ishida, Yoichi Kawasaki, Hisashi Matsunaga & Toshiaki Sendo

  2. Department of Clinical Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan

    Shigeru Ishida & Hiromu Kawasaki

  3. Department of Clinical Pharmacology and Pharmacy, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan

    Hiroaki Araki

  4. Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Masato Asanuma

  5. School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan

    Yutaka Gomita

  6. Department of Pharmaceutical Care and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Yoshihisa Kitamura

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  1. Shigeru Ishida
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  2. Yoichi Kawasaki
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  7. Hiromu Kawasaki
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  8. Yutaka Gomita
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  9. Yoshihisa Kitamura
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Correspondence to Yoshihisa Kitamura.

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Ishida, S., Kawasaki, Y., Araki, H. et al. α7 Nicotinic acetylcholine receptors in the central amygdaloid nucleus alter naloxone-induced withdrawal following a single exposure to morphine. Psychopharmacology 214, 923–931 (2011). https://doi.org/10.1007/s00213-010-2101-7

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  • DOI: https://doi.org/10.1007/s00213-010-2101-7

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