α-Conotoxin TxID and [S9K]TxID, α3β4 NAChR Antagonists, Attenuate Expression and Reinstatement of Nicotine-Induced Conditioned Place Preference in Mice

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2020 Dec 19

PMID 33339145

Citations 2

Authors

Xiaodan Li

Shen You

Jian Xiong

Yamin Qiao

Jinpeng Yu

Dongting Zhangsun

Sulan Luo

Affiliations

Soon will be listed here.

Abstract

Tobacco smoking has become a prominent health problem faced around the world. The α3β4 nicotinic acetylcholine receptor (nAChR) is strongly associated with nicotine reward and withdrawal symptom. α-Conotoxin TxID, cloned from Conus textile, is a strong α3β4 nAChR antagonist, which has weak inhibition activity of α6/α3β4 nAChR. Meanwhile, its analogue [S9K]TxID only inhibits α3β4 nAChR (IC = 6.9 nM), and has no inhibitory activity to other nAChRs. The present experiment investigates the effect of α3β4 nAChR antagonists (TxID and [S9K]TxID) on the expression and reinstatement of nicotine-induced conditioned place preference (CPP) and explores the behaviors of acute nicotine in mice. The animal experimental results showed that TxID and [S9K] TxID could inhibit the expression and reinstatement of CPP, respectively. Moreover, both had no effect in acute nicotine experiment and the locomotor activity in mice. Therefore, these findings reveal that the α3β4 nAChR may be a potential target for anti-nicotine addiction treatment. [S9K]TxID, α3β4 nAChR antagonist, exhibit a superior effect for anti-nicotine addiction, which is promising to develop a novel smoking cessation drug.

Citing Articles

What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.

Straub C, Rusali L, Kremiller K, Riley A J Med Chem. 2022; 66(1):107-121.

PMID: 36440853 PMC: 10034762. DOI: 10.1021/acs.jmedchem.2c01562.

Fluorescently Labeled α-Conotoxin TxID, a New Probe for α3β4 Neuronal Nicotinic Acetylcholine Receptors.

Huang M, Zhu X, Yang Y, Tan Y, Luo S, Zhangsun D Mar Drugs. 2022; 20(8).

PMID: 36005514 PMC: 9410468. DOI: 10.3390/md20080511.

References

Salas R, Pieri F, De Biasi M . Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit. J Neurosci. 2004; 24(45):10035-9. PMC: 6730195. DOI: 10.1523/JNEUROSCI.1939-04.2004. View

Ware J, van den Bree M, Munafo M . Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis. Nicotine Tob Res. 2011; 13(12):1167-75. PMC: 3223575. DOI: 10.1093/ntr/ntr118. View

Costello M, Reynaga D, Mojica C, Zaveri N, Belluzzi J, Leslie F . Comparison of the reinforcing properties of nicotine and cigarette smoke extract in rats. Neuropsychopharmacology. 2014; 39(8):1843-51. PMC: 4059892. DOI: 10.1038/npp.2014.31. View

Nordberg A, Hellstrom-Lindahl E, Lee M, Johnson M, Mousavi M, Hall R . Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw). J Neurochem. 2002; 81(3):655-8. DOI: 10.1046/j.1471-4159.2002.00874.x. View

Cippitelli A, Wu J, Gaiolini K, Mercatelli D, Schoch J, Gorman M . AT-1001: a high-affinity α3β4 nAChR ligand with novel nicotine-suppressive pharmacology. Br J Pharmacol. 2014; 172(7):1834-45. PMC: 4376460. DOI: 10.1111/bph.13034. View

Hernandez S, Vicini S, Xiao Y, Davila-Garcia M, Yasuda R, Wolfe B . The nicotinic receptor in the rat pineal gland is an alpha3beta4 subtype. Mol Pharmacol. 2004; 66(4):978-87. DOI: 10.1124/mol.104.002345. View

Frahm S, Slimak M, Ferrarese L, Santos-Torres J, Antolin-Fontes B, Auer S . Aversion to nicotine is regulated by the balanced activity of β4 and α5 nicotinic receptor subunits in the medial habenula. Neuron. 2011; 70(3):522-35. DOI: 10.1016/j.neuron.2011.04.013. View

Toll L, Zaveri N, Polgar W, Jiang F, Khroyan T, Zhou W . AT-1001: a high affinity and selective α3β4 nicotinic acetylcholine receptor antagonist blocks nicotine self-administration in rats. Neuropsychopharmacology. 2012; 37(6):1367-76. PMC: 3327842. DOI: 10.1038/npp.2011.322. View

You S, Li X, Xiong J, Zhu X, Zhangsun D, Zhu X . α-Conotoxin TxIB: A Uniquely Selective Ligand for α6/α3β2β3 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Conditioned Place Preference in Mice. Mar Drugs. 2019; 17(9). PMC: 6780885. DOI: 10.3390/md17090490. View

10.

Jackson K, McIntosh J, Brunzell D, Sanjakdar S, Damaj M . The role of alpha6-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal. J Pharmacol Exp Ther. 2009; 331(2):547-54. PMC: 2775251. DOI: 10.1124/jpet.109.155457. View

11.

McCallum S, Cowe M, Lewis S, Glick S . α3β4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in vivo. Neuropharmacology. 2012; 63(3):434-40. PMC: 3381928. DOI: 10.1016/j.neuropharm.2012.04.015. View

12.

Sack R, Gochberg-Sarver A, Rozovsky U, Kedmi M, Rosner S, Orr-Urtreger A . Lower core body temperature and attenuated nicotine-induced hypothermic response in mice lacking the beta4 neuronal nicotinic acetylcholine receptor subunit. Brain Res Bull. 2005; 66(1):30-6. DOI: 10.1016/j.brainresbull.2005.02.032. View

13.

Salas R, Cook K, Bassetto L, De Biasi M . The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology. 2004; 47(3):401-7. DOI: 10.1016/j.neuropharm.2004.05.002. View

14.

Reus V, Smith B . Multimodal techniques for smoking cessation: a review of their efficacy and utilisation and clinical practice guidelines. Int J Clin Pract. 2008; 62(11):1753-68. DOI: 10.1111/j.1742-1241.2008.01885.x. View

15.

Yu J, Zhu X, Harvey P, Kaas Q, Zhangsun D, Craik D . Single Amino Acid Substitution in α-Conotoxin TxID Reveals a Specific α3β4 Nicotinic Acetylcholine Receptor Antagonist. J Med Chem. 2018; 61(20):9256-9265. DOI: 10.1021/acs.jmedchem.8b00967. View

16.

Glick S, Sell E, McCallum S, Maisonneuve I . Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration. Eur J Pharmacol. 2011; 669(1-3):71-5. PMC: 3183297. DOI: 10.1016/j.ejphar.2011.08.001. View

17.

Gorlich A, Antolin-Fontes B, Ables J, Frahm S, Slimak M, Dougherty J . Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons. Proc Natl Acad Sci U S A. 2013; 110(42):17077-82. PMC: 3800986. DOI: 10.1073/pnas.1313103110. View

18.

Semenova S, Contet C, Roberts A, Markou A . Mice lacking the β4 subunit of the nicotinic acetylcholine receptor show memory deficits, altered anxiety- and depression-like behavior, and diminished nicotine-induced analgesia. Nicotine Tob Res. 2012; 14(11):1346-55. PMC: 3482014. DOI: 10.1093/ntr/nts107. View

19.

Dellu F, Piazza P, Mayo W, Le Moal M, Simon H . Novelty-seeking in rats--biobehavioral characteristics and possible relationship with the sensation-seeking trait in man. Neuropsychobiology. 1996; 34(3):136-45. DOI: 10.1159/000119305. View

20.

Paulus M, Dulawa S, Ralph R, Geyer M . Behavioral organization is independent of locomotor activity in 129 and C57 mouse strains. Brain Res. 1999; 835(1):27-36. DOI: 10.1016/s0006-8993(99)01137-3. View