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Chronic treatment with a metabotropic mGlu2/3 receptor agonist diminishes behavioral response to a phenethylamine hallucinogen

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Abstract

Background

There is evidence that mGlu2/3 receptors regulate 5-HT2A signaling, interactions that have been theorized to play a role in the antipsychotic-like effects of mGlu2/3 agonists as well as the hallucinogenic effects of 5-HT2A agonists. One approach to unraveling this interaction is through the chronic administration of agonists at the two receptors, which should influence the functional properties of the targeted receptor due to receptor downregulation or desensitization and thereby alter crosstalk between the two receptors. In this study, we investigated whether chronic treatment with the mGlu2/3 agonist LY379268 would alter the behavioral response to a phenethylamine hallucinogen, 25CN-NBOH, which acts as a selective 5-HT2A agonist.

Methods

We first conducted a dose response of 25CN-NBOH (0.1, 0.3, 1, 3, or 10 mg/kg) to confirm the effects on head-twitch response (HTR) and then blockade studies with either the M100907 (0.1 mg/kg) or SB242084 (0.1, 0.3, or 1 mg/kg) to determine the contribution of 5-HT2A and 5-HT2C to 25CN-NBOH-induced HTR, respectively. To determine whether an mGlu2/3 agonist could block 25CN-NBOH-induced HTR, mice were pretreated with vehicle or LY379268 (0.1, 1, or 10 mg/kg) prior to 25CN-NBOH, and HTR was assessed. The effects of chronic LY379268 on 5-HT2A agonist-induced HTR were evaluated by treating mice with either vehicle or LY379268 (10 mg/kg) for 21 days and measuring 25CN-NBOH-induced HTR 48 h after the final LY379268 treatment. The following day (72 h after the final LY379268 treatment), the ability of acute LY379268 to block PCP-induced locomotor activity was assessed.

Results

25CN-NBOH dose-dependently increased the HTR, a 5-HT2A-mediated behavior, in mice. The selective 5-HT2A antagonist M100907 completely blocked the HTR induced by 25CN-NBOH, whereas the selective 5-HT2C antagonist SB242084 had no effect on the HTR. Administration of LY379268 (10 mg/kg SC) attenuated the HTR induced by 1 mg/kg 25CN-NBOH by ~ 50%. Chronic treatment (21 days) with LY379268 also attenuated the HTR response to 25CN-NBOH when tested 48 h after the last dose of LY379268. In locomotor tests, acute LY379268 significantly attenuated PCP-induced locomotor activity in the chronic vehicle treatment group; by contrast, there was only a trend for an overall interaction in the chronic LY379268 group, with LY379268 blocking the locomotor-stimulating effects of PCP only during the last 20 min.

Conclusions

These data are consistent with a functional interaction between mGlu2/3 and 5-HT2A receptors, although the specific mechanism for the interaction is not known. These data support the hypothesis that mGlu2/3 receptors play a prominent role in modulating the behavioral response to 5-HT2A receptor activation.

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References

  • Aghajanian GK, Marek GJ (1999) Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release. Brain Res 825:161–171

    Article  CAS  PubMed  Google Scholar 

  • Benneyworth MA, Smith RL, Sanders-Bush E (2008) Chronic phenethylamine hallucinogen treatment alters behavioral sensitivity to a metabotropic glutamate 2/3 receptor agonist. Neuropsychopharmacology 33:2206–2216

    Article  CAS  PubMed  Google Scholar 

  • Benneyworth MA, Xiang Z, Smith RL, Garcia EE, Conn PJ, Sanders-Bush E (2007) A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis. Mol Pharmacol 72:477–484

    Article  CAS  PubMed  Google Scholar 

  • Benvenga MJ, Chaney SF, Baez M, Britton TC, Hornback WJ, Monn JA, Marek GJ (2018) Metabotropic glutamate2 receptors play a key role in modulating head twitches induced by a serotonergic hallucinogen in mice. Front Pharmacol 9:208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bond A, Jones NM, Hicks CA, Whiffin GM, Ward MA, O’Neill MF, Kingston AE, Monn JA, Ornstein PL, Schoepp DD, Lodge D, O’Neill MJ (2000) Neuroprotective effects of LY379268, a selective mGlu2/3 receptor agonist: investigations into possible mechanism of action in vivo. J Pharmacol Exp Ther 294:800–809

    CAS  PubMed  Google Scholar 

  • Buchborn T, Lyons T, Knopfel T (2018) Tolerance and tachyphylaxis to head twitches induced by the 5-HT2A agonist 25CN-NBOH in mice. Front Pharmacol 9:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canal CE, Morgan D (2012) Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model. Drug Test Anal 4:556–576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB (2015) The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice. Psychopharmacology 232:275–284

    Article  CAS  PubMed  Google Scholar 

  • Cartmell J, Monn JA, Schoepp DD (1999) The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats. J Pharmacol Exp Ther 291:161–170

    CAS  PubMed  Google Scholar 

  • Cartmell J, Perry KW, Salhoff CR, Monn JA, Schoepp DD (2001) Acute increases in monoamine release in the rat prefrontal cortex by the mGlu2/3 agonist LY379268 are similar in profile to risperidone, not locally mediated, and can be elicited in the presence of uptake blockade. Neuropharmacology 40:847–855

    Article  CAS  PubMed  Google Scholar 

  • Chartoff EH, Heusner CL, Palmiter RD (2005) Dopamine is not required for the hyperlocomotor response to NMDA receptor antagonists. Neuropsychopharmacology 30:1324–1333

    Article  CAS  PubMed  Google Scholar 

  • Christopoulos A, Grant MK, Ayoubzadeh N, Kim ON, Sauerberg P, Jeppesen L, El-Fakahany EE (2001) Synthesis and pharmacological evaluation of dimeric muscarinic acetylcholine receptor agonists. J Pharmacol Exp Ther 298:1260–1268

    CAS  PubMed  Google Scholar 

  • Conn PJ, Jones CK (2009) Promise of mGluR2/3 activators in psychiatry. Neuropsychopharmacology 34:248–249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delille HK, Becker JM, Burkhardt S, Bleher B, Terstappen GC, Schmidt M, Meyer AH, Unger L, Marek GJ, Mezler M (2012) Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. Neuropharmacology 62:2184–2191

    Article  CAS  PubMed  Google Scholar 

  • Delille HK, Mezler M, Marek GJ (2013) The two faces of the pharmacological interaction of mGlu2 and 5-HT(2)A - relevance of receptor heterocomplexes and interaction through functional brain pathways. Neuropharmacology 70:296–305

    Article  CAS  PubMed  Google Scholar 

  • Downing AM, Kinon BJ, Millen BA, Zhang L, Liu L, Morozova MA, Brenner R, Rayle TJ, Nisenbaum L, Zhao F, Gomez JC (2014) A double-blind, placebo-controlled comparator study of LY2140023 monohydrate in patients with schizophrenia. BMC Psychiatry 14:351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egashira N, Shirakawa A, Okuno R, Mishima K, Iwasaki K, Oishi R, Fujiwara M (2011) Role of endocannabinoid and glutamatergic systems in DOI-induced head-twitch response in mice. Pharmacol Biochem Behav 99:52–58

    Article  CAS  PubMed  Google Scholar 

  • Fantegrossi WE, Gray BW, Bailey JM, Smith DA, Hansen M, Kristensen JL (2015) Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT(2)A receptors, in mice. Psychopharmacology 232:1039–1047

    Article  CAS  PubMed  Google Scholar 

  • Fantegrossi WE, Simoneau J, Cohen MS, Zimmerman SM, Henson CM, Rice KC, Woods JH (2010) Interaction of 5-HT2A and 5-HT2C receptors in R(−)-2,5-dimethoxy-4-iodoamphetamine-elicited head twitch behavior in mice. J Pharmacol Exp Ther 335:728–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fribourg M, Moreno JL, Holloway T, Provasi D, Baki L, Mahajan R, Park G, Adney SK, Hatcher C, Eltit JM, Ruta JD, Albizu L, Li Z, Umali A, Shim J, Fabiato A, MacKerell AD Jr, Brezina V, Sealfon SC, Filizola M, Gonzalez-Maeso J, Logothetis DE (2011) Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell 147:1011–1023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galici R, Echemendia NG, Rodriguez AL, Conn PJ (2005) A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity. J Pharmacol Exp Ther 315:1181–1187

    Article  CAS  PubMed  Google Scholar 

  • Gewirtz JC, Marek GJ (2000) Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors. Neuropsychopharmacology 23:569–576

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452:93–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA (2007) Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron 53:439–452

    Article  CAS  PubMed  Google Scholar 

  • Gorzalka BB, Hill MN, Sun JC (2005) Functional role of the endocannabinoid system and AMPA/kainate receptors in 5-HT2A receptor-mediated wet dog shakes. Eur J Pharmacol 516:28–33

    Article  CAS  PubMed  Google Scholar 

  • Halberstadt AL (2015) Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behav Brain Res 277:99–120

    Article  CAS  PubMed  Google Scholar 

  • Halberstadt AL, Geyer MA (2013) Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement. Psychopharmacology 227:727–739

    Article  CAS  PubMed  Google Scholar 

  • Halberstadt AL, Geyer MA (2014) Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response. Neuropharmacology 77:200–207

    Article  CAS  PubMed  Google Scholar 

  • Halberstadt AL, Powell SB, Geyer MA (2013) Role of the 5-HT(2)a receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice. Neuropharmacology 70:218–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halberstadt AL, Sindhunata IS, Scheffers K, Flynn AD, Sharp RF, Geyer MA, Young JW (2016) Effect of 5-HT2A and 5-HT2C receptors on temporal discrimination by mice. Neuropharmacology 107:364–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halberstadt AL, van der Heijden I, Ruderman MA, Risbrough VB, Gingrich JA, Geyer MA, Powell SB (2009) 5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice. Neuropsychopharmacology

  • Hansen M, Phonekeo K, Paine JS, Leth-Petersen S, Begtrup M, Brauner-Osborne H, Kristensen JL (2014) Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists. ACS Chem Neurosci 5:243–249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iacovelli L, Molinaro G, Battaglia G, Motolese M, Di Menna L, Alfiero M, Blahos J, Matrisciano F, Corsi M, Corti C, Bruno V, De Blasi A, Nicoletti F (2009) Regulation of group II metabotropic glutamate receptors by G protein-coupled receptor kinases: mGlu2 receptors are resistant to homologous desensitization. Mol Pharmacol 75:991–1003

    Article  CAS  PubMed  Google Scholar 

  • Jensen AA, McCorvy JD, Leth-Petersen S, Bundgaard C, Liebscher G, Kenakin TP, Brauner-Osborne H, Kehler J, Kristensen JL (2017) Detailed characterization of the in vitro pharmacological and pharmacokinetic properties of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (25CN-NBOH), a highly selective and brain-penetrant 5-HT2A receptor agonist. J Pharmacol Exp Ther 361:441–453

    Article  CAS  PubMed  Google Scholar 

  • Kinon BJ, Zhang L, Millen BA, Osuntokun OO, Williams JE, Kollack-Walker S, Jackson K, Kryzhanovskaya L, Jarkova N (2011) A multicenter, inpatient, phase 2, double-blind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol 31:349–355

    Article  CAS  PubMed  Google Scholar 

  • Klein LM, Cozzi NV, Daley PF, Brandt SD, Halberstadt AL (2018) Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs. Neuropharmacology

  • Klodzinska A, Bijak M, Tokarski K, Pilc A (2002) Group II mGlu receptor agonists inhibit behavioural and electrophysiological effects of DOI in mice. Pharmacol Biochem Behav 73:327–332

    Article  CAS  PubMed  Google Scholar 

  • Kurita M, Moreno JL, Holloway T, Kozlenkov A, Mocci G, Garcia-Bea A, Hanks JB, Neve R, Nestler EJ, Russo SJ, Gonzalez-Maeso J (2013) Repressive epigenetic changes at the mGlu2 promoter in frontal cortex of 5-HT2A knockout mice. Mol Pharmacol 83:1166–1175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Jamba M, Patrick C 3rd, Padmanabhan S, Brennan MD (2012) Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study. Pharmacogenomics 13:1227–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA (2003) Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117:697–706

    Article  CAS  PubMed  Google Scholar 

  • Marek GJ, Wright RA, Schoepp DD (2006) 5-Hydroxytryptamine2A (5-HT2A) receptor regulation in rat prefrontal cortex: interaction of a phenethylamine hallucinogen and the metabotropic glutamate2/3 receptor agonist LY354740. Neurosci Lett 403:256–260

    Article  CAS  PubMed  Google Scholar 

  • Marek GJ, Wright RA, Schoepp DD, Monn JA, Aghajanian GK (2000) Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex. J Pharmacol Exp Ther 292:76–87

    CAS  PubMed  Google Scholar 

  • Moghaddam B, Adams BW (1998) Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281:1349–1352

    Article  CAS  PubMed  Google Scholar 

  • Molinaro G, Traficante A, Riozzi B, Di Menna L, Curto M, Pallottino S, Nicoletti F, Bruno V, Battaglia G (2009) Activation of mGlu2/3 metabotropic glutamate receptors negatively regulates the stimulation of inositol phospholipid hydrolysis mediated by 5-hydroxytryptamine2A serotonin receptors in the frontal cortex of living mice. Mol Pharmacol 76:379–387

    Article  CAS  PubMed  Google Scholar 

  • Moreno JL, Holloway T, Albizu L, Sealfon SC, Gonzalez-Maeso J (2011) Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett 493:76–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moreno JL, Holloway T, Rayannavar V, Sealfon SC, Gonzalez-Maeso J (2013) Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice. Neurosci Lett 536:69–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuellar F, Mocci G, Seto J, Callado LF, Neve RL, Milligan G, Sealfon SC, Lopez-Gimenez JF, Meana JJ, Benson DL, Gonzalez-Maeso J (2012) Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its psychoactive behavioral function. J Biol Chem 287:44301–44319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nichols DE (2004) Hallucinogens. Pharmacol Ther 101:131–181

    Article  CAS  PubMed  Google Scholar 

  • Nichols DE, Sassano MF, Halberstadt AL, Klein LM, Brandt SD, Elliott SP, Fiedler WJ (2015) N-Benzyl-5-methoxytryptamines as potent serotonin 5-HT receptor family agonists and comparison with a series of phenethylamine analogues. In: ACS Chem Neurosci

    Google Scholar 

  • Nisenbaum LK, Downing AM, Zhao F, Millen BA, Munsie L, Kinon BJ, Adams DH, Gomez JC, Penny MA (2016) Serotonin 2A receptor SNP rs7330461 association with treatment response to pomaglumetad methionil in patients with schizophrenia. J Pers Med 6

  • Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD (2007) Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat Med 13:1102–1107

    Article  CAS  PubMed  Google Scholar 

  • Pei Q, Tordera R, Sprakes M, Sharp T (2004) Glutamate receptor activation is involved in 5-HT2 agonist-induced Arc gene expression in the rat cortex. Neuropharmacology 46:331–339

    Article  CAS  PubMed  Google Scholar 

  • Riga MS, Soria G, Tudela R, Artigas F, Celada P (2014) The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs. Int J Neuropsychopharmacol 17:1269–1282

    Article  CAS  PubMed  Google Scholar 

  • Sanders-Bush E, Breeding M, Knoth K, Tsutsumi M (1989) Sertraline-induced desensitization of the serotonin 5HT-2 receptor transmembrane signaling system. Psychopharmacology 99:64–69

    Article  CAS  PubMed  Google Scholar 

  • Schoepp DD (2001) Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 299:12–20

    CAS  PubMed  Google Scholar 

  • Scruggs JL, Patel S, Bubser M, Deutch AY (2000) DOI-induced activation of the cortex: dependence on 5-HT2A heteroceptors on thalamocortical glutamatergic neurons. J Neurosci 20:8846–8852

    Article  CAS  PubMed  Google Scholar 

  • Wieronska JM, Slawinska A, Stachowicz K, Lason-Tyburkiewicz M, Gruca P, Papp M, Pilc A (2013) The reversal of cognitive, but not negative or positive symptoms of schizophrenia, by the mGlu(2)/(3) receptor agonist, LY379268, is 5-HT(1)A dependent. Behav Brain Res 256:298–304

    Article  CAS  PubMed  Google Scholar 

  • Winter JC, Eckler JR, Rabin RA (2004) Serotonergic/glutamatergic interactions: the effects of mGlu2/3 receptor ligands in rats trained with LSD and PCP as discriminative stimuli. Psychopharmacology 172:233–240

    Article  CAS  PubMed  Google Scholar 

  • Wischhof L, Koch M (2012) Pre-treatment with the mGlu2/3 receptor agonist LY379268 attenuates DOI-induced impulsive responding and regional c-Fos protein expression. Psychopharmacology 219:387–400

    Article  CAS  PubMed  Google Scholar 

  • Yamada S, Watanabe A, Nankai M, Toru M (1995) Acute immobilization stress reduces (+/−)DOI-induced 5-HT2A receptor-mediated head shakes in rats. Psychopharmacology 119:9–14

    Article  CAS  PubMed  Google Scholar 

  • Zhai Y, George CA, Zhai J, Nisenbaum ES, Johnson MP, Nisenbaum LK (2003) Group II metabotropic glutamate receptor modulation of DOI-induced c-fos mRNA and excitatory responses in the cerebral cortex. Neuropsychopharmacology 28:45–52

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Marek GJ (2008) AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes. Prog Neuro-Psychopharmacol Biol Psychiatry 32:62–71

    Article  CAS  Google Scholar 

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Acknowledgments

We would like to thank Landon Klein and Mahalah Buell for the technical assistance. LY379268 was generously supplied by the NIMH Chemical Synthesis and Drug Supply Program (CSDSP). These studies were supported by R01 DA002925, R01 DA041336, K01 MH100644, and Veteran’s Affairs VISN 22 MIRECC.

Funding

These studies were supported by R01 DA002925, R01 DA041336, K01 MH100644, and Veteran’s Affairs VISN 22 MIRECC.

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Authors and Affiliations

  1. Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0804, USA

    Adam L. Halberstadt, Jochem V. F. van der Zee, Muhammad Chatha, Mark A. Geyer & Susan B. Powell

  2. Research Service, VA San Diego Healthcare System, La Jolla, CA, USA

    Adam L. Halberstadt, Mark A. Geyer & Susan B. Powell

  3. Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands

    Jochem V. F. van der Zee

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  1. Adam L. Halberstadt
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  2. Jochem V. F. van der Zee
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  3. Muhammad Chatha
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  5. Susan B. Powell
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Correspondence to Susan B. Powell.

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Mark Geyer holds an equity interest in San Diego Instruments.

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Halberstadt, A.L., van der Zee, J.V.F., Chatha, M. et al. Chronic treatment with a metabotropic mGlu2/3 receptor agonist diminishes behavioral response to a phenethylamine hallucinogen. Psychopharmacology 236, 821–830 (2019). https://doi.org/10.1007/s00213-018-5118-y

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