Chronic Nicotine Exposure Alters Metabotropic Glutamate Receptor 5: Longitudinal PET Study and Behavioural Assessment in Rats

Overview

Journal Neurotox Res

Publisher Springer

Specialty Neurology

Date 2019 May 24

PMID 31119680

Citations 4

Authors

Adrienne Muller Herde

Yoan Mihov

Stefanie D Kramer

Linjing Mu

Antoine Adamantidis

Simon M Ametamey

Gregor Hasler

Affiliations

Soon will be listed here.

Abstract

Using positron emission tomography (PET), a profound alteration of the metabotropic glutamate receptor 5 (mGluR5) was found in human smoking addiction and abstinence. As human PET data either reflect the impact of chronic nicotine exposure or a pre-existing vulnerability to nicotine addiction, we designed a preclinical, longitudinal study to investigate the effect of chronic nicotine exposure on mGluR5 with the novel radiotracer [F]PSS232 using PET. Twelve male dark Agouti rats at the age of 6 weeks were assigned randomly to three groups. From day 0 to day 250 the groups received 0 mg/L, 4 mg/L, or 8 mg/L nicotine solution in the drinking water. From day 250 to 320 all groups received nicotine-free drinking water. PET scans with [F]PSS232 were performed in all animals on days 0, 250, and 320. To assess locomotion, seven tests in square open field arenas were carried out 72 days after the last PET scan. During the first four tests, rats received 0 mg/L nicotine and for the last three tests 4 mg/L nicotine in the drinking water. After 250 days of nicotine consumption [F]PSS232 binding was reduced in the striatum, hippocampus, thalamus, and midbrain. At day 320, after nicotine withdrawal, [F]PSS232 binding increased. These effects were more pronounced in the 4 mg/L nicotine group. Chronic administration of nicotine through the drinking water reduced exploratory behaviour. This preliminary longitudinal PET study demonstrates that chronic nicotine administration alters behaviour and mGluR5 availability. Chronic nicotine administration leads to decreased [F]PSS232 binding which normalizes after prolonged nicotine withdrawal.

Citing Articles

Smoking affects symptom improvement in schizophrenia: a prospective longitudinal study of male patients with first-episode schizophrenia.

Mu X, Wu W, Wang S, Su X, Guan H, Guan X Schizophrenia (Heidelb). 2024; 10(1):34.

PMID: 38491003 PMC: 10943037. DOI: 10.1038/s41537-024-00449-1.

Demographics, clinical characteristics and cognitive symptoms of heavy smokers and non-heavy smokers in Chinese male patients with chronic schizophrenia.

Wei S, Wang D, Zhou H, Xia L, Tian Y, Dai Q Eur Arch Psychiatry Clin Neurosci. 2022; 272(7):1325-1333.

PMID: 35474549 DOI: 10.1007/s00406-022-01410-y.

Multidimensional Intersection of Nicotine, Gene Expression, and Behavior.

Sherafat Y, Bautista M, Fowler C Front Behav Neurosci. 2021; 15:649129.

PMID: 33828466 PMC: 8019722. DOI: 10.3389/fnbeh.2021.649129.

Allosteric modulation of metabotropic glutamate receptors in alcohol use disorder: Insights from preclinical investigations.

Johnson K, Lovinger D Adv Pharmacol. 2020; 88:193-232.

PMID: 32416868 PMC: 7384598. DOI: 10.1016/bs.apha.2020.02.002.

References

. Annual smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 1997-2001. MMWR Morb Mortal Wkly Rep. 2005; 54(25):625-8. View

Olive M . Metabotropic glutamate receptor ligands as potential therapeutics for addiction. Curr Drug Abuse Rev. 2009; 2(1):83-98. PMC: 2717506. DOI: 10.2174/1874473710902010083. View

Kita T, Nakashima T, Kurogochi Y . Effects of oral administration of nicotine on circadian rhythms of ambulatory activity and drinking in rats. Jpn J Pharmacol. 1985; 39(4):554-7. DOI: 10.1254/jjp.39.554. View

Ametamey S, Kessler L, Honer M, Wyss M, Buck A, Hintermann S . Radiosynthesis and preclinical evaluation of 11C-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5. J Nucl Med. 2006; 47(4):698-705. View

Hamilton K, Starosciak A, Chwa A, Grunberg N . Nicotine behavioral sensitization in Lewis and Fischer male rats. Exp Clin Psychopharmacol. 2012; 20(5):345-51. DOI: 10.1037/a0029088. View

Milicevic Sephton S, Muller Herde A, Mu L, Keller C, Rudisuhli S, Auberson Y . Preclinical evaluation and test-retest studies of [(18)F]PSS232, a novel radioligand for targeting metabotropic glutamate receptor 5 (mGlu5). Eur J Nucl Med Mol Imaging. 2014; 42(1):128-37. DOI: 10.1007/s00259-014-2883-7. View

Hulka L, Treyer V, Scheidegger M, Preller K, Vonmoos M, Baumgartner M . Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans. Mol Psychiatry. 2013; 19(5):625-32. DOI: 10.1038/mp.2013.51. View

Collins A, Pogun S, Nesil T, Kanit L . Oral Nicotine Self-Administration in Rodents. J Addict Res Ther. 2012; S2. PMC: 3527900. DOI: 10.4172/2155-6105.S2-004. View

Barr D, Levy R, Scheepers C, Tily H . Random effects structure for confirmatory hypothesis testing: Keep it maximal. J Mem Lang. 2014; 68(3). PMC: 3881361. DOI: 10.1016/j.jml.2012.11.001. View

10.

Ametamey S, Treyer V, Streffer J, Wyss M, Schmidt M, Blagoev M . Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688. J Nucl Med. 2007; 48(2):247-52. View

11.

Gaddnas H, Pietila K, Ahtee L . Effects of chronic oral nicotine treatment and its withdrawal on locomotor activity and brain monoamines in mice. Behav Brain Res. 2000; 113(1-2):65-72. DOI: 10.1016/s0166-4328(00)00201-1. View

12.

Akkus F, Treyer V, Ametamey S, Johayem A, Buck A, Hasler G . Metabotropic glutamate receptor 5 neuroimaging in schizophrenia. Schizophr Res. 2016; 183:95-101. DOI: 10.1016/j.schres.2016.11.008. View

13.

Emmitte K . mGlu negative allosteric modulators: a patent review (2013 - 2016). Expert Opin Ther Pat. 2017; 27(6):691-706. DOI: 10.1080/13543776.2017.1280466. View

14.

Akkus F, Ametamey S, Treyer V, Burger C, Johayem A, Umbricht D . Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [11C]ABP688 positron emission tomography. Proc Natl Acad Sci U S A. 2012; 110(2):737-42. PMC: 3545768. DOI: 10.1073/pnas.1210984110. View

15.

Marszalek-Grabska M, Gibula-Bruzda E, Bodzon-Kulakowska A, Suder P, Gawel K, Filarowska J . Effects of the Positive Allosteric Modulator of Metabotropic Glutamate Receptor 5, VU-29, on Impairment of Novel Object Recognition Induced by Acute Ethanol and Ethanol Withdrawal in Rats. Neurotox Res. 2018; 33(3):607-620. PMC: 5871646. DOI: 10.1007/s12640-017-9857-z. View

16.

Muller Herde A, Keller C, Milicevic Sephton S, Mu L, Schibli R, Ametamey S . Quantitative positron emission tomography of mGluR5 in rat brain with [(18) F]PSS232 at minimal invasiveness and reduced model complexity. J Neurochem. 2014; 133(3):330-42. DOI: 10.1111/jnc.13001. View

17.

Catania M, DAntoni S, Bonaccorso C, Aronica E, Bear M, Nicoletti F . Group I metabotropic glutamate receptors: a role in neurodevelopmental disorders?. Mol Neurobiol. 2007; 35(3):298-307. DOI: 10.1007/s12035-007-0022-1. View

18.

Welzl H, Alessandri B, Oettinger R, Batig K . The effects of long-term nicotine treatment on locomotion, exploration and memory in young and old rats. Psychopharmacology (Berl). 1988; 96(3):317-23. DOI: 10.1007/BF00216057. View

19.

Wijetunge L, Till S, Gillingwater T, Ingham C, Kind P . mGluR5 regulates glutamate-dependent development of the mouse somatosensory cortex. J Neurosci. 2008; 28(49):13028-37. PMC: 3844741. DOI: 10.1523/JNEUROSCI.2600-08.2008. View

20.

Yu M, Fu W, Yin H . Effect of amphetamine on the expression of the metabotropic glutamate receptor 5 mRNA in developing rat brain. J Mol Neurosci. 2001; 15(3):177-88. DOI: 10.1385/JMN:15:3:177. View