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Role of Metabotropic Glutamate Receptors in Alcohol-Drinking Behaviors

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Metabotropic Glutamate Receptor Technologies

Part of the book series: Neuromethods ((NM,volume 164))

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Abstract

Glutamatergic system impairments have been associated with long-term use of drugs of abuse, including alcohol. Metabotropic glutamate receptors (mGlus) have been suggested to be involved in drug addiction and other neuropsychiatric disorders. Different subtypes of mGlus have been considered to be implicated in certain neuropsychiatric disorders, including substance use disorders. Chronic uses of these drugs have been found to alter the function and expression of mGlus. For example, increases in mGlu1 expression in the nucleus accumbens (NAc) were found in animals exposed to either alcohol or nicotine. However, the expression of mGlu2/3 is decreased in the NAc following chronic exposure to alcohol. Importantly, pharmacological studies showed that mGlu1/5 antagonists and mGlu2/3 agonists attenuated alcohol intake and relapse-like alcohol-drinking behaviors. Furthermore, new technologies, such as optogenetics, have been used to investigate the regulatory roles of mGlu isoforms in the mesocorticolimbic brain areas in animals exposed to alcohol. In this book chapter, we discussed the effects of alcohol exposure using different drinking paradigms on the expression and function of mGlus and the pharmacological manipulations (via agonists or antagonists) of mGlus in alcohol-seeking and relapse to alcohol-like behaviors.

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References

  1. Behar D, Berg CJ, Rapoport JL, Nelson W, Linnoila M, Cohen M et al (1983) Behavioral and physiological effects of ethanol in high-risk and control children: a pilot study. Alcohol Clin Exp Res 7(4):404–410

    Article  CAS  PubMed  Google Scholar 

  2. Preedy V, Adachi J, Ueno Y, Ahmed S, Mantle D, Mullatti N et al (2001) Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis. Eur J Neurol 8(6):677–687

    Article  CAS  PubMed  Google Scholar 

  3. Wilson GT, Abrams D (1977) Effects of alcohol on social anxiety and physiological arousal: cognitive versus pharmacological processes. Cogn Ther Res 1(3):195–210

    Article  Google Scholar 

  4. Alfonso-Loeches S, Pascual M, Guerri C (2013) Gender differences in alcohol-induced neurotoxicity and brain damage. Toxicology 311(1–2):27–34

    Article  CAS  PubMed  Google Scholar 

  5. Tiwari V, Kuhad A, Chopra K (2012) Neuroprotective effect of vitamin E isoforms against chronic alcohol-induced peripheral neurotoxicity: possible involvement of oxidative-Nitrodative stress. Phytother Res 26(11):1738–1745

    Article  CAS  PubMed  Google Scholar 

  6. Alhaddad H, Kim NT, Aal-Aaboda M, Althobaiti YS, Leighton J, Boddu SH et al (2014) Effects of MS-153 on chronic ethanol consumption and GLT1 modulation of glutamate levels in male alcohol-preferring rats. Front Behav Neurosci 8:366

    Article  PubMed  PubMed Central  Google Scholar 

  7. Laguesse S, Morisot N, Phamluong K, Ron D (2017) Region specific activation of the AKT and mTORC1 pathway in response to excessive alcohol intake in rodents. Addict Biol 22(6):1856–1869

    Article  CAS  PubMed  Google Scholar 

  8. Tiwari V, Chopra K (2013) Protective effect of curcumin against chronic alcohol-induced cognitive deficits and neuroinflammation in the adult rat brain. Neuroscience 244:147–158

    Article  CAS  PubMed  Google Scholar 

  9. Griffin WC III, Haun HL, Hazelbaker CL, Ramachandra VS, Becker HC (2014) Increased extracellular glutamate in the nucleus accumbens promotes excessive ethanol drinking in ethanol dependent mice. Neuropsychopharmacology 39(3):707

    Article  CAS  PubMed  Google Scholar 

  10. Hakami AY, Hammad AM, Sari Y (2016) Effects of amoxicillin and augmentin on cystine-glutamate exchanger and glutamate transporter 1 isoforms as well as ethanol intake in alcohol-preferring rats. Front Neurosci 10:171

    Article  PubMed  PubMed Central  Google Scholar 

  11. Goodwani S, Rao P, Bell RL, Sari Y (1622) Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT-1 expression as well as AKT phosphorylation in mesocorticolimbic regions. Brain Res 2015:397–408

    Google Scholar 

  12. Das SC, Yamamoto BK, Hristov AM, Sari Y (2015) Ceftriaxone attenuates ethanol drinking and restores extracellular glutamate concentration through normalization of GLT-1 in nucleus accumbens of male alcohol-preferring rats. Neuropharmacology 97:67–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. LaCrosse AL, O’Donovan SM, Sepulveda-Orengo MT, McCullumsmith RE, Reissner KJ, Schwendt M et al (2017) Contrasting the role of xCT and GLT-1 upregulation in the ability of ceftriaxone to attenuate the cue-induced reinstatement of cocaine seeking and normalize AMPA receptor subunit expression. J Neurosci 37(24):5809–5821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rao P, Saternos H, Goodwani S, Sari Y (2015) Effects of ceftriaxone on GLT1 isoforms, xCT and associated signaling pathways in P rats exposed to ethanol. Psychopharmacology 232(13):2333–2342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tanabe Y, Masu M, Ishii T, Shigemoto R, Nakanishi S (1992) A family of metabotropic glutamate receptors. Neuron 8(1):169–179

    Article  CAS  PubMed  Google Scholar 

  16. Conn PJ, Pin J-P (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37(1):205–237

    Article  CAS  PubMed  Google Scholar 

  17. Baudry M, Greget R, Pernot F, Bouteiller JM, Xiaoning B (2012) Roles of group I metabotropic glutamate receptors under physiological conditions and in neurodegeneration. Wiley Interdiscip Rev 1(4):523–532

    CAS  Google Scholar 

  18. Lum EN, Campbell RR, Rostock C, Szumlinski KK (2014) mGluR1 within the nucleus accumbens regulates alcohol intake in mice under limited-access conditions. Neuropharmacology 79:679–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cozzoli DK, Courson J, Caruana AL, Miller BW, Greentree DI, Thompson AB et al (2012) Nucleus Accumbens m G lu R 5-associated signaling regulates binge alcohol drinking under drinking-in-the-dark procedures. Alcohol Clin Exp Res 36(9):1623–1633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Blednov YA, Adron HR (2008) Metabotropic glutamate receptor 5 (mGluR5) regulation of ethanol sedation, dependence and consumption: relationship to acamprosate actions. Int J Neuropsychopharmacol 11(6):775–793

    Article  CAS  PubMed  Google Scholar 

  21. Cozzoli DK, Courson J, Wroten MG, Greentree DI, Lum EN, Campbell RR et al (2014) Binge alcohol drinking by mice requires intact group1 metabotropic glutamate receptor signaling within the central nucleus of the amygdale. Neuropsychopharmacology 39(2):435

    Article  CAS  PubMed  Google Scholar 

  22. Besheer J, Faccidomo S, Grondin JJ, Hodge CW (2008) Regulation of motivation to self-administer ethanol by mGluR5 in alcohol-preferring (P) rats. Alcohol Clin Exp Res 32(2):209–221

    Article  CAS  PubMed  Google Scholar 

  23. Cozzoli DK, Strong-Kaufman MN, Tanchuck MA, Hashimoto JG, Wiren KM, Finn DA (2014) The effect of mGluR 5 antagonism during binge drinking on subsequent ethanol intake in C 57 BL/6 J mice: sex-and age-induced differences. Alcohol Clin Exp Res 38(3):730–738

    Article  CAS  PubMed  Google Scholar 

  24. Besheer J, Faccidomo S, Grondin J, Hodge C (2008) Effects of mGlu1-receptor blockade on ethanol self-administration in inbred alcohol-preferring rats. Alcohol 42(1):13–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schroeder JP, Spanos M, Stevenson JR, Besheer J, Salling M, Hodge CW (2008) Cue-induced reinstatement of alcohol-seeking behavior is associated with increased ERK1/2 phosphorylation in specific limbic brain regions: blockade by the mGluR5 antagonist MPEP. Neuropharmacology 55(4):546–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bäckström P, Bachteler D, Koch S, Hyytiä P, Spanagel R (2004) mGluR5 antagonist MPEP reduces ethanol-seeking and relapse behavior. Neuropsychopharmacology 29(5):921

    Article  PubMed  CAS  Google Scholar 

  27. Alasmari F, Bell RL, Rao P, Hammad AM, Sari Y (2018) Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats. Pharmacol Biochem Behav 170:44–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Leurquin-Sterk G, Crunelle C, Ceccarini J, de Laat B, Peuskens H, Bormans G et al (2016) Alcohol addiction is associated with decreased limbic mGluR5 availability: a 18F-FPEB PET study in human. J Nucl Med 57(supplement 2):15

    Google Scholar 

  29. Leurquin-Sterk G, Ceccarini J, Crunelle CL, de Laat B, Verbeek J, Deman S et al (2018) Lower limbic metabotropic glutamate receptor 5 availability in alcohol dependence. J Nucl Med 59(4):682–690

    Article  CAS  PubMed  Google Scholar 

  30. Smith KS, Bucci DJ, Luikart BW, Mahler SV (2016) DREADDS: use and application in behavioral neuroscience. Behav Neurosci 130(2):137

    Article  PubMed  PubMed Central  Google Scholar 

  31. Xu Y, Li Z (2019) Imaging metabotropic glutamate receptor system: application of positron emission tomography technology in drug development. Med Res Rev 39:1892

    Article  PubMed  Google Scholar 

  32. Mahler SV, Hensley-Simon M, Tahsili-Fahadan P, LaLumiere RT, Thomas C, Fallon RV et al (2014) Modafinil attenuates reinstatement of cocaine seeking: role for cystine–glutamate exchange and metabotropic glutamate receptors. Addict Biol 19(1):49–60

    Article  CAS  PubMed  Google Scholar 

  33. Moran MM, McFarland K, Melendez RI, Kalivas PW, Seamans JK (2005) Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking. J Neurosci 25(27):6389–6393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Reissner KJ, Kalivas PW (2010) Using glutamate homeostasis as a target for treating addictive disorders. Behav Pharmacol 21(5–6):514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Augier E, Dulman RS, Rauffenbart C, Augier G, Cross AJ, Heilig M (2016) The mGluR2 positive allosteric modulator, AZD8529, and cue-induced relapse to alcohol seeking in rats. Neuropsychopharmacology 41(12):2932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhou Z, Karlsson C, Liang T, Xiong W, Kimura M, Tapocik JD et al (2013) Loss of metabotropic glutamate receptor 2 escalates alcohol consumption. Proc Natl Acad Sci U S A 110(42):16963–16968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhao Y, Dayas CV, Aujla H, Baptista MA, Martin-Fardon R, Weiss F (2006) Activation of group II metabotropic glutamate receptors attenuates both stress and cue-induced ethanol-seeking and modulates c-fos expression in the hippocampus and amygdala. J Neurosci 26(39):9967–9974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sidhpura N, Weiss F, Martin-Fardon R (2010) Effects of the mGlu2/3 agonist LY379268 and the mGlu5 antagonist MTEP on ethanol seeking and reinforcement are differentially altered in rats with a history of ethanol dependence. Biol Psychiatry 67(9):804–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bäckström P, Hyytiä P (2005) Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3, 4-DCPG. Eur J Pharmacol 528(1–3):110–118

    Article  PubMed  CAS  Google Scholar 

  40. Laukkanen V, Kärkkäinen O, Kupila J, Kautiainen H, Tiihonen J, Storvik M (2014) Increased metabotropic glutamate 2/3 receptor binding in the perigenual anterior cingulate cortex of Cloninger type 2 alcoholics: a whole-hemisphere autoradiography study. Alcohol Alcohol 50(1):62–67

    Article  PubMed  CAS  Google Scholar 

  41. Meinhardt MW, Hansson AC, Perreau-Lenz S, Bauder-Wenz C, Stählin O, Heilig M et al (2013) Rescue of infralimbic mGluR2 deficit restores control over drug-seeking behavior in alcohol dependence. J Neurosci 33(7):2794–2806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Goodwani S, Saternos H, Alasmari F, Sari Y (2017) Metabotropic and ionotropic glutamate receptors as potential targets for the treatment of alcohol use disorder. Neurosci Biobehav Rev 77:14–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Vardi N, Duvoisin R, Wu G, Sterling P (2000) Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. J Comp Neurol 423(3):402–412

    Article  CAS  PubMed  Google Scholar 

  44. Ueda Y, Iwakabe H, Masu M, Suzuki M, Nakanishi S (1997) The mGluR6 5′ upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal rod and ON-type cone bipolar cells. J Neurosci 17(9):3014–3023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Salling MC, Faccidomo S, Hodge CW (2008) Nonselective suppression of operant ethanol and sucrose self-administration by the mGluR7 positive allosteric modulator AMN082. Pharmacol Biochem Behav 91(1):14–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bahi A (2012) The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 prevents reinstatement of extinguished ethanol-induced conditioned place preference in mice. Pharmacol Biochem Behav 101(2):193–200

    Article  CAS  PubMed  Google Scholar 

  47. Akkus F, Mihov Y, Treyer V, Ametamey SM, Johayem A, Senn S et al (2018) Metabotropic glutamate receptor 5 binding in male patients with alcohol use disorder. Transl Psychiatry 8(1):17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Wang K-W, Ye X-L, Huang T, Yang X-F, Zou L-Y (2019) Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer’s disease. Neural Regen Res 14(12):2147

    Article  PubMed  PubMed Central  Google Scholar 

  49. Purohit K, Parekh PK, Kern J, Logan RW, Liu Z, Huang Y et al (2018) Pharmacogenetic manipulation of the nucleus Accumbens alters binge-like alcohol drinking in mice. Alcohol Clin Exp Res 42(5):879–888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Manvich DF, Webster KA, Foster SL, Farrell MS, Ritchie JC, Porter JH et al (2018) The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. Sci Rep 8(1):3840

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. McGeehan AJ, Olive MF (2003) The mGluR5 antagonist MPEP reduces the conditioned rewarding effects of cocaine but not other drugs of abuse. Synapse 47(3):240–242

    Article  CAS  PubMed  Google Scholar 

  52. Paterson NE, Semenova S, Gasparini F, Markou A (2003) The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice. Psychopharmacology 167(3):257–264

    Article  CAS  PubMed  Google Scholar 

  53. Gass JT, Osborne MP, Watson NL, Brown JL, Olive MF (2009) mGluR5 antagonism attenuates methamphetamine reinforcement and prevents reinstatement of methamphetamine-seeking behavior in rats. Neuropsychopharmacology 34(4):820

    Article  CAS  PubMed  Google Scholar 

  54. Achat-Mendes C, Platt DM, Spealman RD (2012) Antagonism of metabotropic glutamate 1 receptors attenuates behavioral effects of cocaine and methamphetamine in squirrel monkeys. J Pharmacol Exp Ther 343(1):214–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dravolina OA, Zakharova ES, Shekunova EV, Zvartau EE, Danysz W, Bespalov AY (2007) mGlu1 receptor blockade attenuates cue-and nicotine-induced reinstatement of extinguished nicotine self-administration behavior in rats. Neuropharmacology 52(2):263–269

    Article  CAS  PubMed  Google Scholar 

  56. Schroeder JP, Overstreet DH, Hodge CW (2005) The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats. Psychopharmacology 179(1):262–270

    Article  CAS  PubMed  Google Scholar 

  57. Hodge CW, Miles MF, Sharko AC, Stevenson RA, Hillmann JR, Lepoutre V et al (2006) The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Psychopharmacology 183(4):429–438

    Article  CAS  PubMed  Google Scholar 

  58. Cozzoli DK, Goulding SP, Zhang PW, Xiao B, Hu J-H, Ary AW et al (2009) Binge drinking upregulates accumbens mGluR5–Homer2–PI3K signaling: functional implications for alcoholism. J Neurosci 29(27):8655–8668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Obara I, Bell RL, Goulding SP, Reyes CM, Larson LA, Ary AW et al (2009) Differential effects of chronic ethanol consumption and withdrawal on homer/glutamate receptor expression in subregions of the accumbens and amygdala of P rats. Alcohol Clin Exp Res 33(11):1924–1934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jin X, Semenova S, Yang L, Ardecky R, Sheffler DJ, Dahl R et al (2010) The mGluR2 positive allosteric modulator BINA decreases cocaine self-administration and cue-induced cocaine-seeking and counteracts cocaine-induced enhancement of brain reward function in rats. Neuropsychopharmacology 35(10):2021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Justinova Z, Panlilio LV, Secci ME, Redhi GH, Schindler CW, Cross AJ et al (2015) The novel metabotropic glutamate receptor 2 positive allosteric modulator, AZD8529, decreases nicotine self-administration and relapse in squirrel monkeys. Biol Psychiatry 78(7):452–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Windisch KA, Czachowski CL (2018) Effects of group II metabotropic glutamate receptor modulation on ethanol-and sucrose-seeking and consumption in the rat. Alcohol 66:77–85

    Article  CAS  PubMed  Google Scholar 

  63. Justinova Z, Le Foll B, Redhi GH, Markou A, Goldberg SR (2016) Differential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on nicotine versus cocaine self-administration and relapse in squirrel monkeys. Psychopharmacology 233(10):1791–1800

    Article  CAS  PubMed  Google Scholar 

  64. Cannella N, Halbout B, Uhrig S, Evrard L, Corsi M, Corti C et al (2013) The mGluR2/3 agonist LY379268 induced anti-reinstatement effects in rats exhibiting addiction-like behavior. Neuropsychopharmacology 38(10):2048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Griebel G, Pichat P, Boulay D, Naimoli V, Potestio L, Featherstone R et al (2016) The mGluR2 positive allosteric modulator, SAR218645, improves memory and attention deficits in translational models of cognitive symptoms associated with schizophrenia. Sci Rep 6:35320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kufahl PR, Martin-Fardon R, Weiss F (2011) Enhanced sensitivity to attenuation of conditioned reinstatement by the mGluR 2/3 agonist LY379268 and increased functional activity of mGluR 2/3 in rats with a history of ethanol dependence. Neuropsychopharmacology 36(13):2762–2773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Rodd ZA, McKinzie DL, Bell RL, McQueen VK, Murphy JM, Schoepp DD et al (2006) The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats. Behav Brain Res 171(2):207–215

    Article  CAS  PubMed  Google Scholar 

  68. Enoch MA, Rosser AA, Zhou Z, Mash DC, Yuan Q, Goldman D (2014) Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine. Genes Brain Behav 13(8):758–768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Cannady R, Grondin JJ, Fisher KR, Hodge CW, Besheer J (2011) Activation of group II metabotropic glutamate receptors inhibits the discriminative stimulus effects of alcohol via selective activity within the amygdala. Neuropsychopharmacology 36(11):2328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lainiola M, Hietala L, Linden A-M, Aitta-aho T (2019) The lack of conditioned place preference, but unaltered stimulatory and ataxic effects of alcohol in mGluR3-KO mice. J Psychopharmacol 33(7):855–864

    Article  CAS  PubMed  Google Scholar 

  71. Bahi A, Fizia K, Dietz M, Gasparini F, Flor PJ (2012) Pharmacological modulation of mGluR7 with AMN082 and MMPIP exerts specific influences on alcohol consumption and preference in rats. Addict Biol 17(2):235–247

    Article  CAS  PubMed  Google Scholar 

  72. Vadasz C, Saito M, Gyetvai BM, Oros M, Szakall I, Kovacs KM et al (2007) Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking. Genomics 90(6):690–702

    Article  CAS  PubMed  Google Scholar 

  73. Blednov YA, Walker D, Osterndorf-Kahanek E, Harris RA (2004) Mice lacking metabotropic glutamate receptor 4 do not show the motor stimulatory effect of ethanol. Alcohol 34(2–3):251–259

    Article  CAS  PubMed  Google Scholar 

  74. Stuber GD, Sparta DR, Stamatakis AM, van Leeuwen WA, Hardjoprajitno JE, Cho S et al (2011) Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nature 475(7356):377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Millan EZ, Kim HA, Janak PH (2017) Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior. Neuroscience 360:106–117

    Article  CAS  PubMed  Google Scholar 

  76. Benn A, Barker GR, Stuart SA, Roloff EVL, Teschemacher AG, Warburton EC et al (2016) Optogenetic stimulation of prefrontal glutamatergic neurons enhances recognition memory. J Neurosci 36(18):4930–4939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Robins MT, Chiang T, Mores KL, Alongkronrusmee D, Van Rijn RM (2018) Critical role for Gi/o-protein activity in the dorsal striatum in the reduction of voluntary alcohol intake in C57BL/6 mice. Front Psychol 9:112

    Article  Google Scholar 

  78. Hermann D, Weber-Fahr W, Sartorius A, Hoerst M, Frischknecht U, Tunc-Skarka N et al (2012) Translational magnetic resonance spectroscopy reveals excessive central glutamate levels during alcohol withdrawal in humans and rats. Biol Psychiatry 71(11):1015–1021

    Article  CAS  PubMed  Google Scholar 

  79. Kärkkäinen O, Kupila J, Häkkinen M, Laukkanen V, Tupala E, Kautiainen H et al (2013) AMPA receptors in post-mortem brains of Cloninger type 1 and 2 alcoholics: a whole-hemisphere autoradiography study. Psychiatry Res Neuroimaging 214(3):429–434

    Article  Google Scholar 

  80. Levitz J, Pantoja C, Gaub B, Janovjak H, Reiner A, Hoagland A et al (2013) Optical control of metabotropic glutamate receptors. Nat Neurosci 16(4):507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would to thank the National Institutes of Health (R01AA019458 to Y.S.) and the International Scientific Partnership Program (ISPP-146) from the deanship of scientific research, King Saud University, for their support.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Fawaz Alasmari & Musaad A. Alshammari

  2. Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA

    Youssef Sari

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  1. Fawaz Alasmari
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  2. Musaad A. Alshammari
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  3. Youssef Sari
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Correspondence to Fawaz Alasmari or Youssef Sari .

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Editors and Affiliations

  1. Psychology Department, Arizona State University, Tempe, AZ, USA

    M Foster Olive

  2. Phoenix Children’s Hospital, Barrow Neurological Institute, Phoenix, AZ, USA

    Brian T. Burrows

  3. Psychology Department, Arizona State University, Tempe, AZ, USA

    Jonna M. Leyrer-Jackson

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Alasmari, F., Alshammari, M.A., Sari, Y. (2021). Role of Metabotropic Glutamate Receptors in Alcohol-Drinking Behaviors. In: Olive, M.F., Burrows, B.T., Leyrer-Jackson, J.M. (eds) Metabotropic Glutamate Receptor Technologies. Neuromethods, vol 164. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1107-4_14

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  • DOI: https://doi.org/10.1007/978-1-0716-1107-4_14

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