Partial mGlu 5 Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects

Neuropsychopharmacology

Volumn 41, Issue 4, 2016, Pages 1166-1178

  Gould, Robert W ^a,c   Amato, Russell J ^a,c   Bubser, Michael ^a   Joffe, Max E ^a   Nedelcovych, Michael T ^a   Thompson, Analisa D ^a   Nickols, Hilary H ^a,b   Yuh, Johannes P ^a   Zhan, Xiaoyan ^a   Felts, Andrew S ^a,b   Rodriguez, Alice L ^a   Morrison, Ryan D ^a   Byers, Frank W ^a   Rook, Jerri M ^a   Daniels, John S ^a   Niswender, Colleen M ^a   Conn, P Jeffrey ^a   Emmitte, Kyle A ^a,b   Lindsley, Craig W ^a,b   Jones, Carrie K ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^c LOUISIANA STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 3 [(2 METHYL 4 THIAZOLYL)ETHYNYL]PYRIDINE; METABOTROPIC RECEPTOR 5; 2-(2-(3-METHOXYPHENYL)ETHYNYL)-5-METHYLPYRIDINE; 3-((2-METHYL-1,3-THIAZOL-4-YL)ETHYNYL)PYRIDINE; ALKYNE; ANTIDEPRESSANT AGENT; ANXIOLYTIC AGENT; COCAINE; PHENCYCLIDINE; PYRIDINE DERIVATIVE; THIAZOLE DERIVATIVE;

ADULT; ALLOSTERISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIDEPRESSANT ACTIVITY; ARTICLE; BRAIN HOMOGENATE; BRAIN LEVEL; BRAIN-TO-PLASMA RATIO; COCAINE DEPENDENCE; COMPARATIVE STUDY; CONTROLLED STUDY; DISCRIMINATIVE STIMULUS; FORCED SWIM TEST; HIPPOCAMPAL TISSUE; IN VIVO STUDY; LOCOMOTION; MALE; MARBLE BURYING TEST; MOTOR ACTIVITY; NONHUMAN; PLACE PREFERENCE; PRIORITY JOURNAL; RAT; REINFORCEMENT; TAIL SUSPENSION TEST; THERAPEUTIC INDEX; TRANQUILIZING ACTIVITY; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN; CONDITIONED REFLEX; DOSE RESPONSE; DRUG EFFECTS; DRUG SEEKING BEHAVIOR; DRUG SELF ADMINISTRATION; INSTRUMENTAL CONDITIONING; MOUSE; SPRAGUE DAWLEY RAT;

ALKYNES; ALLOSTERIC REGULATION; ANIMALS; ANTI-ANXIETY AGENTS; ANTIDEPRESSIVE AGENTS; BRAIN; COCAINE; CONDITIONING, CLASSICAL; CONDITIONING, OPERANT; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG-SEEKING BEHAVIOR; MALE; MICE; MOTOR ACTIVITY; PHENCYCLIDINE; PYRIDINES; RATS, SPRAGUE-DAWLEY; RECEPTOR, METABOTROPIC GLUTAMATE 5; SELF ADMINISTRATION; THIAZOLES;

EID: 84957594483     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2015.265     Document Type: Article

References (70)

1. Administration SAMHSA (2012). Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings. NSDUH: Rockville, MD. Vol Series H-44, HHS Publication No (SMA) 12-4713.
2. Amato RJ, Felts AS, Rodriguez AL, Venable DF, Morrison RD, Byers FW et al (2013). Substituted 1-Phenyl-3-(pyridin-2-yl)urea negative allosteric modulators of mGlu5: discovery of a new tool compound VU0463841 with activity in rat models of cocaine addiction. ACS Chem Neurosci 4: 1217-1228.
3. Anderson JJ, Bradbury MJ, Giracello DR, Chapman DF, Holtz G, Roppe J et al (2003). In vivo receptor occupancy of mGlu5 receptor antagonists using the novel radioligand [3H]3-methoxy-5-(pyridin-2-ylethynyl)pyridine). Eur J Pharmacol 473: 35-40.
4. Backstrom P, Hyytia P (2006). Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. Neuropsychopharmacology 31: 778-786.
5. Ballard TM, Woolley ML, Prinssen E, Huwyler J, Porter R, Spooren W (2005). The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and cognition: A comparison. Psychopharmacology (Berl) 179: 218-229.
6. Berg D, Godau J, Trenkwalder C, Eggert K, Csoti I, Storch A et al (2011). AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials. Mov Disord 26: 1243-1250.
7. Bird MK, Lawrence AJ (2009). The promiscuous mGlu5 receptor-A range of partners for therapeutic possibilities? Trends Pharmacol Sci 30: 617-623.
8. Borsini F, Podhorna J, Marazziti D (2002). Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology (Berl) 163: 121-141.
9. Brady KT, Verduin ML, Tolliver BK (2007). Treatment of patients comorbid for addiction and other psychiatric disorders. Curr Psychiatry Rep 9: 374-380.
10. Brown RM, Duncan JR, Stagnitti MR, Ledent C, Lawrence AJ (2012). mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine. Int J Neuropsychopharmacol 15: 995-1001.
11. Bubser M, Bridges TM, Dencker D, Gould RW, Grannan M, Noetzel MJ et al (2014). Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci 5: 920-942.
12. Busse CS, Brodkin J, Tattersall D, Anderson JJ, Warren N, Tehrani L et al (2004). The behavioral profile of the potent and selective mGlu5 receptor antagonist 3-[(2-methyl-1, 3-Thiazol-4-yl)ethynyl]pyridine (MTEP) in rodent models of anxiety. Neuropsychopharmacology 29: 1971-1979.
13. Byun NE, Grannan M, Bubser M, Barry RL, Thompson A, Rosanelli J et al (2014). Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100. Neuropsychopharmacology 39: 1578-1593.
14. Christopoulos A (2014). Advances in G protein-coupled receptor allostery: from function to structure. Mol Pharmacol 86: 463-478.
15. Conn PJ, Christopoulos A, Lindsley CW (2009). Allosteric modulators of GPCRs: A novel approach for the treatment of CNS disorders. Nat Rev Drug Discov 8: 41-54.
16. Cosford ND, Tehrani L, Roppe J, Schweiger E, Smith ND, Anderson J et al (2003). 3-[(2-Methyl-1, 3-Thiazol-4-yl)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity. J Med Chem 46: 204-206.
17. Coyle JT (2012). NMDA receptor and schizophrenia: A brief history. Schizophr Bull 38: 920-926.
18. Crowley JJ, Blendy JA, Lucki I (2005). Strain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test. Psychopharmacology (Berl) 183: 257-264.
19. Emmitte KA (2011). Recent advances in the design and development of novel negative allosteric modulators of mGlu(5). ACS Chem Neurosci 2: 411-432.
20. Felts AS, Rodriguez AL, Morrison RD, Venable DF, Manka JT, Bates BS et al (2013). Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg Med Chem Lett 23: 5779-5785.
21. Friedmann CTH, Davis LJ, Cicione PE, Rubin RT (1980). Phase II double-blind controlled study for a new anxiolytic, Fenobam (McN-3377) vs placebo. Curr Ther Res 27: 144-151.
22. Fujii S, Mikoshiba K, Kuroda Y, Ahmed TM, Kato H (2003). Cooperativity between activation of metabotropic glutamate receptors and NMDA receptors in the induction of LTP in hippocampal CA1 neurons. Neurosci Res 46: 509-521.
23. Gasparini F, Lingenhohl K, Stoehr N, Flor PJ, Heinrich M, Vranesic I et al (1999). 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 38: 1493-1503.
24. Golembiowska K, Konieczny J, Wolfarth S, Ossowska K (2003). Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats. Neuropharmacology 45: 484-492.
25. Goudet C, Gaven F, Kniazeff J, Vol C, Liu J, Cohen-Gonsaud M et al (2004). Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors. Proc Natl Acad Sci USA 101: 378-383.
26. Gravius A, Pietraszek M, Schafer D, Schmidt WJ, Danysz W (2005). Effects of mGlu1 and mGlu5 receptor antagonists on negatively reinforced learning. Behav Pharmacol 16: 113-121.
27. Gravius A, Pietraszek M, Schmidt WJ, DanyszW(2006). Functional interaction of NMDA and group I metabotropic glutamate receptors in negatively reinforced learning in rats. Psychopharmacology (Berl) 185: 58-65.
28. Gurkovskaya OV, Winsauer PJ (2009). Discriminative stimulus effects of ethanol, pregnanolone, and dehydroepiandrosterone (DHEA) in rats administered ethanol or saline as adolescents. Pharmacol Biochem Behav 93: 82-90.
29. Henry SA, Lehmann-Masten V, Gasparini F, Geyer MA, Markou A (2002). The mGluR5 antagonist MPEP, but not the mGluR2/3 agonist LY314582, augments PCP effects on prepulse inhibition and locomotor activity. Neuropharmacology 43: 1199-1209.
30. Herzig V, Schmidt WJ (2004). Effects of MPEP on locomotion, sensitization and conditioned reward induced by cocaine or morphine. Neuropharmacology 47: 973-984.
31. Hiranita T, Soto PL, Tanda G, Katz JL (2010). Reinforcing effects of sigma-receptor agonists in rats trained to self-Administer cocaine. J Pharmacol Exp Ther 332: 515-524.
32. Homayoun H, Stefani MR, Adams BW, Tamagan GD, Moghaddam B (2004). Functional interaction between NMDA and mGlu5 receptors: effects on working memory, instrumental learning, motor behaviors, and dopamine release. Neuropsychopharmacology 29: 1259-1269.
33. Hughes ZA, Neal SJ, Smith DL, Sukoff Rizzo SJ, Pulicicchio CM, Lotarski S et al (2013). Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression. Neuropharmacology 66: 202-214.
34. Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ et al (2011). Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med 3: 64ra61.
35. Jones CK, Brady AE, Davis AA, Xiang Z, Bubser M, Tantawy MN et al (2008). Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. J Neurosci 28: 10422-10433.
36. Keck TM, Yang HJ, Bi GH, Huang Y, Zhang HY, Srivastava R et al (2013). Fenobam sulfate inhibits cocaine-Taking and cocaineseeking behavior in rats: implications for addiction treatment in humans. Psychopharmacology (Berl) 229: 253-265.
37. Keck TM, ZouMF, Bi GH, ZhangHY, WangXF, Yang HJ et al (2014). A novel mGluR5 antagonist, MFZ 10-7, inhibits cocaine-Taking and cocaine-seeking behavior in rats. Addict Biol 19: 195-209.
38. Keck TM, Zou MF, Zhang P, Rutledge RP, Newman AH (2012). Metabotropic glutamate receptor 5 negative allosteric modulators as novel tools for in vivo investigation. ACS Med Chem Lett 3: 544-549.
39. Kenny PJ, Boutrel B, Gasparini F, Koob GF, Markou A (2005). Metabotropic glutamate 5 receptor blockade may attenuate cocaine self-Administration by decreasing brain reward function in rats. Psychopharmacology (Berl) 179: 247-254.
40. Kinney GG, Burno M, Campbell UC, Hernandez LM, Rodriguez D, Bristow LJ et al (2003). Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents. J Pharmacol Exp Ther 306: 116-123.
41. Kishi T, Matsuda Y, Iwata N, Correll CU (2013). Antipsychotics for cocaine or psychostimulant dependence: systematic review and meta-Analysis of randomized, placebo-controlled trials. J Clin Psychiatry 74: e1169-e1180.
42. Kumaresan V, Yuan M, Yee J, Famous KR, Anderson SM, Schmidt HD et al (2009). Metabotropic glutamate receptor 5 (mGluR5) antagonists attenuate cocaine priming-And cueinduced reinstatement of cocaine seeking. Behav Brain Res 202: 238-244.
43. Lee B, Platt DM, Rowlett JK, Adewale AS, Spealman RD (2005). Attenuation of behavioral effects of cocaine by the metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)-pyridine in squirrel monkeys: comparison with dizocilpine. J Pharmacol Exp Ther 312: 1232-1240.
44. Lindemann L, Porter RH, Scharf SH, Kuennecke B, Bruns A, von Kienlin M et al (2015). Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. J Pharmacol Exp Ther 353: 213-233.
45. Mannaioni G, Marino MJ, Valenti O, Traynelis SF, Conn PJ (2001). Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci 21: 5925-5934.
46. Marino MJ, Conn PJ (2002). Direct and indirect modulation of the N-methyl D-Aspartate receptor. Curr Drug Targets CNS Neurol Disord 1: 1-16.
47. McGeehan AJ, Olive MF (2003). The mGluR5 antagonist MPEP reduces the conditioned rewarding effects of cocaine but not other drugs of abuse. Synapse 47: 240-242.
48. Moore TJ, Glenmullen J, Mattison DR (2014). Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med 174: 1930-1933.
49. Nickols HH, Conn PJ (2014). Development of allosteric modulators of GPCRs for treatment of CNS disorders. Neurobiol Dis 61: 55-71.
50. Niswender CM, Conn PJ (2010). Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50: 295-322.
51. Noetzel MJ, Gregory KJ, Vinson PN, Manka JT, Stauffer SR, Lindsley CW et al (2013). A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling. Mol Pharmacol 83: 835-847.
52. Paterson NE, Markou A (2005). The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats. Psychopharmacology (Berl) 179: 255-261.
53. Pecknold JC, McClure DJ, Appeltauer L, Wrzesinski L, Allan T (1982). Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double-blind standard (diazepam) placebo-controlled study. J Clin Psychopharmacol 2: 129-133.
54. Pietraszek M, Rogoz Z, Wolfarth S, Ossowska K (2004). Opposite influence of MPEP, an mGluR5 antagonist, on the locomotor hyperactivity induced by PCP and amphetamine. J Physiol Pharmacol 55: 587-593.
55. Pisani A, Gubellini P, Bonsi P, Conquet F, Picconi B, Centonze D et al (2001). Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-Aspartate responses in medium spiny striatal neurons. Neuroscience 106: 579-587.
56. Porter RH, Jaeschke G, Spooren W, Ballard TM, Buttelmann B, Kolczewski S et al (2005). Fenobam: A clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity. J Pharmacol Exp Ther 315: 711-721.
57. Rodriguez AL, Grier MD, Jones CK, Herman EJ, Kane AS, Smith RL et al (2010). Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol Pharmacol 78: 1105-1123.
58. Rodriguez AL, Nong Y, Sekaran NK, Alagille D, Tamagnan GD, Conn PJ (2005). A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulators. Mol Pharmacol 68: 1793-1802.
59. Rook JM, Tantawy MN, AnsariMS, Felts AS, Stauffer SR, Emmitte KA et al (2015). Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles. Neuropsychopharmacology 40: 755-765.
60. Roppe JR, Wang B, Huang D, Tehrani L, Kamenecka T, Schweiger EJ et al (2004). 5-[(2-Methyl-1, 3-Thiazol-4-yl)ethynyl]-2, 3'-bipyridine: A highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity. Bioorg Med Chem Lett 14: 3993-3996.
61. Rutten K, Van Der Kam EL, De Vry J, BruckmannW, Tzschentke TM (2011). The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates conditioned place preference induced by various addictive and non-Addictive drugs in rats. Addict Biol 16: 108-115.
62. Shorter D, Domingo CB, Kosten TR (2015). Emerging drugs for the treatment of cocaine use disorder: A review of neurobiological targets and pharmacotherapy. Expert Opin Emerg Drugs 20: 15-29.
63. Swedberg MD, Ellgren M, Raboisson P (2014). mGluR5 antagonistinduced psychoactive properties: MTEP drug discrimination, a pharmacologically selective non-NMDA effect with apparent lack of reinforcing properties. J Pharmacol Exp Ther 349: 155-164.
64. Terbeck S, Akkus F, Chesterman LP, Hasler G (2015). The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies. Front Neurosci 9: 86.
65. Thomsen M, Caine SB (2005). Chronic intravenous drug selfadministration in rats and mice. Curr Protoc Neurosci Chapter 9: Unit 9 20.
66. van der Kam EL, De Vry J, Tzschentke TM (2009). The mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) supports intravenous self-Administration and induces conditioned place preference in the rat. Eur J Pharmacol 607: 114-120.
67. Volkow ND (2004). The reality of comorbidity: depression and drug abuse. Biol Psychiatry 56: 714-717.
68. Vorspan F, Mehtelli W, Dupuy G, Bloch V, Lepine JP (2015). Anxiety and substance use disorders: co-occurrence and clinical issues. Curr Psychiatry Rep 17: 4.
69. Yan HC, Cao X, Das M, Zhu XH, Gao TM (2010). Behavioral animal models of depression. Neurosci Bull 26: 327-337.
70. Young R (2009). Drug discrimination. In: Buccafusco JJ (ed), Methods of Behavior Analysis in Neuroscience, 2nd edn, Chapter 3. CRC Pres: Boca Raton (FL).