- Martin, P. Animal models sensitive to anti-anxiety agents. Acta Psychiatr. Scand. Suppl. 393, 74–80 (1998).
CAS PubMed Google Scholar
- Shekhar, A. et al. Summary of a National Institute of Mental Health workshop: developing animal models of anxiety disorders. Psychopharmacology (Berl). 157, 327–339 (2001). A consensus of experts in the field of anxiety concluded that although current animal models of anxiety are useful for understanding the mechanisms that mediate fear and stress in animals and humans, they are not generally predictive of efficacy in specific diagnostic forms of anxiety in humans.
CAS PubMed Google Scholar
- Woods, J. H., Katz, J. L. & Winger, G. Benzodiazepines: use, abuse, and consequences. Pharmacol. Rev. 44, 151–347 (1992).
CAS PubMed Google Scholar
- Atack, J. R. Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. Curr. Drug Targets CNS Neurol. Disord. 2, 213–232 (2003).
CAS PubMed Google Scholar
- Brunello, N. et al. Noradrenaline in mood and anxiety disorders: basic and clinical studies. Int. Clin. Psychopharmacol. 18, 191–202 (2003).
PubMed Google Scholar
- Gorman, J. M. New molecular targets for antianxiety interventions. J. Clin. Psychiatry 64, 28–35 (2003).
CAS PubMed Google Scholar
- Kehne, J. & De Lombaert, S. Non-peptidic CRF1 receptor antagonists for the treatment of anxiety, depression and stress disorders. Curr. Drug Targets CNS Neurol. Disord. 1, 467–493 (2002).
CAS PubMed Google Scholar
- Holmes, A., Heilig, M., Rupniak, N. M., Steckler, T. & Griebel, G. Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol. Sci. 24, 580–588 (2003).
CAS PubMed Google Scholar
- Vaswani, M., Linda, F. K. & Ramesh, S. Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 85–102 (2003).
CAS PubMed Google Scholar
- Clineschmidt, B. V. Restoration of shock-suppressed behavior by treatment with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev. Res. 2, 147–163 (1982).
CAS Google Scholar
- Wiley, J. L. Behavioral pharmacology of _N_-methyl-D-aspartate antagonists: implications for the study and pharmacotherapy of anxiety and schizophrenia. Exp. Clin. Psychopharmacol. 5, 365–374 (1997).
CAS PubMed Google Scholar
- Danysz, W., Parsons, C. G., Bresnik, I. & Quack, G. Glutamate in CNS disorders. Drug News Perspec. 8, 261–277 (1996).
Google Scholar
- Parsons, C. G. et al. Modulation of NMDA receptors by glycine introduction to some basic aspects and recent developments. Amino Acids 14, 207–216 (1998).
CAS PubMed Google Scholar
- Schoepp, D. D. Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J. Pharmacol. Exp. Ther. 299, 12–20 (2001).
CAS PubMed Google Scholar
- Schoepp, D. D. Novel functions for subtypes of metabotropic glutamate receptors. Neurochem. Int. 24, 439–449 (1994).
CAS PubMed Google Scholar
- Nakanishi, S. Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity. Neuron 13, 1031–1037 (1994).
CAS PubMed Google Scholar
- Pin, J. P. & Acher, F. The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr. Drug Targets CNS Neurol. Disord. 1, 297–317 (2002).
CAS PubMed Google Scholar
- Conn, P. J. & Pin, J. P. Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol. 37, 205–237 (1997).
CAS PubMed Google Scholar
- Swanson, C. J. & Schoepp, D. D. A role for noradrenergic transmission in the actions of phencyclidine and the antipsychotic and antistress effects of mGlu2/3 receptor agonists. Ann. NY Acad. Sci. 1003, 309–317 (2003).
CAS PubMed Google Scholar
- Schoepp, D. D., Wright, R. A., Levine, L. R., Gaydos, B. & Potter, W. Z. LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 6, 189–197 (2003). This paper demonstrated that anxiety associated with CO 2 exposure was reduced by oral administration of LY354740 in human patients with anxiety, thereby showing translation of the anxiolytic effects of LY354740 in the lactate anxiety/panic model in rats.
CAS PubMed Google Scholar
- Gray, J. A. Precision of the neuropsychopharmacology of anxiety: an inquiry into the functions of the septo-hippocampal system. Behav. Brain Sci. 5, 469–534 (1982).
Google Scholar
- Davis, M. The role of the amygdala in fear and anxiety. Annu. Rev. Neurosci. 15, 353–375 (1992).
CAS PubMed Google Scholar
- Ohishi, H., Shigemoto, R., Nakanishi, S. & Mizuno, N. Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat. Neuroscience 53, 1009–1018 (1993).
CAS PubMed Google Scholar
- Ohishi, H., Shigemoto, R., Nakanishi, S. & Mizuno, N. Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: an in situ hybridization study. J. Comp. Neurol. 335, 252–266 (1993).
CAS PubMed Google Scholar
- Petralia, R. S., Wang, Y. X., Niedzielski, A. S. & Wenthold, R. J. The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations. Neuroscience 71, 949–976 (1996).
CAS PubMed Google Scholar
- Wright, R. A., Arnold, M. B., Wheeler, W. J., Ornstein, P. L. & Schoepp, D. D. [3H]LY341495 binding to group II metabotropic glutamate receptors in rat brain. J. Pharmacol. Exp. Ther. 298, 453–460 (2001).
CAS PubMed Google Scholar
- Cartmell, J. & Schoepp, D. D. Regulation of neurotransmitter release by metabotropic glutamate receptors. J. Neurochem. 75, 889–907 (2000).
CAS PubMed Google Scholar
- Anwyl, R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res. Brain Res. Rev. 29, 83–120 (1999).
CAS PubMed Google Scholar
- Tamaru, Y., Nomura, S., Mizuno, N. & Shigemoto, R. Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: differential location relative to pre- and postsynaptic sites. Neuroscience 106, 481–503 (2001).
CAS PubMed Google Scholar
- Helton, D. R., Tizzano, J. P., Monn, J. A., Schoepp, D. D. & Kallman, M. J. Anxiolytic and side-effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate receptors. J. Pharmacol. Exp. Ther. 284, 651–660 (1998). The novel pharmacological profile of LY354740 in animal models of anxiety is described and compared with clinically efffective agents. In particular, LY354740 had similar efficacy to a benzodiazepine in certain models, but with no evidence for CNS depression in benzodiaze-pine-sensitive models of motor function, and of learning and memory.
CAS PubMed Google Scholar
- Walker, D. L. & Davis, M. The role of amygdala glutamate receptors in fear learning, fear-potentiated startle, and extinction. Pharmacol. Biochem. Behav. 71, 379–392 (2002). Report that the actions of LY354740 in the fear-potentiated startle model involves the amygdala, as intra-amygdala injections of the drug reversibly suppressed fear-potentiated startle in rats.
CAS PubMed Google Scholar
- Campeau, S. & Davis, M. Involvement of subcortical and cortical afferents to the lateral nucleus of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli. J. Neurosci. 15, 2312–2327 (1995).
CAS PubMed PubMed Central Google Scholar
- Rainnie, D. G. & Shinnick-Gallagher, P. _Trans_-ACPD and L-APB presynaptically inhibit excitatory glutamatergic transmission in the basolateral amygdala (BLA). Neurosci. Lett. 139, 87–91 (1992).
CAS PubMed Google Scholar
- Pellow, S., Chopin, P., File, S. E. & Briley, M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Methods 14, 149–167 (1985).
CAS PubMed Google Scholar
- Lister, R. G. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl). 92, 180–185 (1987).
CAS PubMed Google Scholar
- Monn, J. A. et al. Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740): a potent, selective, and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties. J. Med. Chem. 40, 528–537 (1997). The synthesis and aspects of structure–activity of LY354740 and its isomers are described. LY354740 was a potent and stereoselective agonist for human and rat mGlu 2 and mGlu 3 receptors in vitro and the actions of LY354740 in models of anxiety showed similar stereoselectivity. The data demonstrated that LY354740 could be used to investigate the therapeutic potential mGlu 2/3 receptor activations in vivo.
CAS PubMed Google Scholar
- Ferris, P., Seward, E. & Dawson, G. R. Interactions between LY354740, a group II metabotropic agonist and the GABA(A)-benzodiazepine receptor complex in the rat elevated plus-maze. J. Psychopharmacol. (Oxf). 15, 76–82 (2001).
CAS Google Scholar
- Engel, J. A., Egbe, P., Liljequist, S. & Soderpalm, B. Effects of amperozide in two animal models of anxiety. Pharmacol. Ther. 64, 429–433 (1989).
CAS Google Scholar
- Nagatani, T. et al. Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative. Psychopharmacology (Berl). 104, 432–438 (1991).
CAS PubMed Google Scholar
- Assie, M. B., Chopin, P., Stenger, A., Palmier, C. & Briley, M. Neuropharmacology of a new potential anxiolytic compound, F 2692, 1-(3′-trifluoromethylphenyl)-1,4-dihydro-3-amino-4-oxo-6-methylpyridazine. 1. Acute and in vitro effects. Psychopharmacology (Berl). 110, 13–18 (1993).
CAS PubMed Google Scholar
- Keim, S. R. & Shekhar, A. Chronic GABA dysfunction in the dorsomedial hypothalamus (DMH) of rats results in a panic-prone state that is NMDA and not non-NMDA receptor-mediated. Soc. Neurosci. Abs. 24, 1674 (1998).
Google Scholar
- Shekhar, A. & Keim, S. R. LY354740, a potent group II metabotropic glutamate receptor agonist prevents lactate-induced panic-like response in panic-prone rats. Neuropharmacology 39, 1139–1146 (2000).
CAS PubMed Google Scholar
- Linden, A. M., Greene, S. J., Bergeron, M. & Schoepp, D. D. Anxiolytic activity of the mGlu2/3 receptor agonist LY354740 on the elevated plus maze is associated with the suppression of stress-induced c-Fos in the hippocampus and increases in c-Fos induction in several other stress-sensitive brain regions. Neuropsychopharmacology 29, 502–513 (2004). The anxiolytic action of LY354740 in mice was associated with highly selective activation of neuronal populations in the mouse brain that included the lateral central amygdala and hippocampus, indicating that these and other associated brain regions mediate the unique pharmacology of mGlu 2/3 receptor agonists.
CAS PubMed Google Scholar
- Beck, C. H. M. & Fibiger, H. C. Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment. J. Neurosci. 15, 709–720 (1995).
CAS PubMed PubMed Central Google Scholar
- Salminen, O., Lahtinen, S. & Ahtee, L. Expression of Fos protein in various rat brain areas following acute nicotine and diazepam. Pharmacol. Biochem. Behav. 54, 241–248 (1996).
CAS PubMed Google Scholar
- Ryabinin, A. E., Criado, J. R., Henriksen, S. J., Bloom, F. & Wilson, M. C. Differential sensitivity of c-Fos expression in hippocampus and other brain regions to moderate and low doses of alcohol. Mol. Psychiatry 2, 32–43 (1997).
CAS PubMed Google Scholar
- Hitzemann, B. & Hitzemann, R. Chlorodiazepoxide-induced expression of c-Fos in the central extended amygdala and other brain regions of the C57BL/6J and DBA/2J inbred mouse strains: relationship to mechanisms of ethanol action. Alcohol. Clin. Exp. Res. 23, 1158–1172 (1999).
CAS PubMed Google Scholar
- Sun, N. & Cassell, M. D. Intrinsic GABAergic neurons in the rat central extended amygdala. J. Comp. Neurol. 330, 381–404 (1993).
CAS PubMed Google Scholar
- Sun, N., Yi, H. & Cassell, M. D. Evidence for a GABAergic interface between coritcal afferents and brainstem projection neurons in the rat central extended amygdala. J. Comp. Neurol. 340, 43–64 (1994).
CAS PubMed Google Scholar
- Veinante, P. & Freund-Mercier, M. -J. Intrinsic and extrinsic connections of the rat central extended amygdala: an in vivo electrophysiological study of the central amygdaloid nucleus. Brain Res. 794, 188–198 (1998).
CAS PubMed Google Scholar
- Olsen, R. W. Drug interactions at the GABA receptor–ionophore complex. Annu. Rev. Pharmacol. Toxicol. 22, 245–277 (1982).
CAS PubMed Google Scholar
- Helton, D. R., Schoepp, D. D., Monn, J. A., Tizzano, J. P. & Kallman, M. J. in Metabotropic Glutamate Receptors in Brain Function (eds. Moroni, F., Nicoletti, F. & Pellegrini-Giampietro, D. E.) 305–314 (Portland, London, 1998).
Google Scholar
- Higgins, G. A. et al. Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent. Neuropharmacology 46, 907–917 (2004).
CAS PubMed Google Scholar
- Moghaddam, B. & Adams, B. W. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281, 1349–1352 (1998). The potential antipsychotic actions of mGlu 2/3 receptor agonists are described in rats, and illustrate that effects in these models are linked to selective suppression of phencyclidine-induced glutamate hyperexcitability. mGlu 2/3 receptors agonists might therefore be useful for clincally testing the glutamate theory of schizophrenia in humans.
CAS PubMed Google Scholar
- Mohler, H., Fritschy, J. M. & Rudolph, U. A new benzodiazepine pharmacology. J. Pharmacol. Exp. Ther. 300, 2–8 (2002).
CAS PubMed Google Scholar
- Low, K. et al. Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290, 131–134 (2000).
CAS PubMed Google Scholar
- Nusser, Z., Sieghart, W., Benke, D., Fritschy, J. M. & Somogyi, P. Differential synaptic localization of two major γ-aminobutyric acid type A receptor α subunits on hippocampal pyramidal cells. Proc. Natl Acad. Sci. USA 93, 11939–11944 (1996).
CAS PubMed PubMed Central Google Scholar
- Fritschy, J. M., Johnson, D. K., Mohler, H. & Rudolph, U. Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo. Neurosci. Lett. 249, 99–102 (1998).
CAS PubMed Google Scholar
- Rudolph, U., Crestani, F. & Mohler, H. GABA(A) receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol. Sci. 22, 188–194 (2001).
CAS PubMed Google Scholar
- Barda, D. A. et al. SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, _N_-(4-phenoxyphenyl)-_N_-(3-pyridinylmethyl)ethanesulfonamide. Bioorg. Med. Chem. Lett. 14, 3099–3102 (2004).
CAS PubMed Google Scholar
- Johnson, M. P. et al. Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor: synthesis and subtype selectivity of _N_-(4-(2-methoxyphenoxy)phenyl)-_N_-(2,2,2- trifluoroethylsulfonyl)pyrid-3-ylmethylamine. J. Med. Chem. 46, 3189–3192 (2003). The discovery of allosteric potentiators of mGlu 2 receptors represented a new approach to finding mGlu receptor subtype-specific agents that are use-dependent and have promise for treating certain CNS disorders, including anxiety.
CAS PubMed Google Scholar
- Johnson, M. P. et al. Biochemical and behavioral characteristics of metabotropic glutamate 2 receptor potentiators. Psychopharmacology (Berl). (in the press).
- Schaffhauser, H. et al. Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol. Pharmacol. 64, 798–810 (2003).
CAS PubMed Google Scholar
- Romano, C. et al. Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J. Comp. Neurol. 355, 455–469 (1995).
CAS PubMed Google Scholar
- Lujan, R., Roberts, J. D., Shigemoto, R., Ohishi, H. & Somogyi, P. Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1α, mGluR2 and mGluR5, relative to neurotransmitter release sites. J. Chem. Neuroanat. 13, 219–241 (1997).
CAS PubMed Google Scholar
- Muly, E. C., Maddox, M. & Smith, Y. Distribution of mGluR1α and mGluR5 immunolabeling in primate prefrontal cortex. J. Comp. Neurol. 467, 521–535 (2003).
CAS PubMed Google Scholar
- Fotuhi, M. et al. Differential localization of phosphoinositide-linked metabotropic glutamate receptor (mGluR1) and the inositol 1,4,5-trisphosphate receptor in rat brain. J. Neurosci. 13, 2001–2012 (1993).
CAS PubMed PubMed Central Google Scholar
- Moroni, F. et al. Presynaptic mGlu1 type receptors potentiate transmitter output in the rat cortex. Eur. J. Pharmacol. 347, 189–195 (1998).
CAS PubMed Google Scholar
- Awad, H., Hubert, G. W., Smith, Y., Levey, A. I. & Conn, P. J. Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus. J. Neurosci. 20, 7871–7879 (2000).
CAS PubMed PubMed Central Google Scholar
- Swanson, C. J., Baker, D. A., Carson, D., Worley, P. F. & Kalivas, P. W. Repeated cocaine administration attenuates group I metabotropic glutamate receptor-mediated glutamate release and behavioral activation: a potential role for Homer. J. Neurosci. 21, 9043–9052 (2001).
CAS PubMed PubMed Central Google Scholar
- Kingston, A. E., Burnett, J. P., Mayne, N. G. & Lodge, D. Pharmacological analysis of 4-carboxyphenylglycine derivatives: comparison of effects on mGluR1α and mGluR5α subtypes. Neuropharmacology 34, 887–894 (1995).
CAS PubMed Google Scholar
- Chojnacka-Wojcik, E., Tatarczynska, E. & Pilc, A. The anxiolytic-like effect of metabotropic glutamate receptor antagonists after intrahippocampal injection in rats. Eur. J. Pharmacol. 319, 153–156 (1997).
CAS PubMed Google Scholar
- Testa, C. M., Standaert, D. G., Young, A. B. & Penney, J. B., Jr. Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat. J. Neurosci. 14, 3005–3018 (1994).
CAS PubMed PubMed Central Google Scholar
- Koch, M. Microinjections of the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-cyclopentane-1,3-dicarboxylate (trans-ACPD) into the amygdala increase the acoustic startle response of rats. Brain Res. 629, 176–179 (1993).
CAS PubMed Google Scholar
- Gasparini, F. et al. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 38, 1493–1503 (1999). The discovery of non-competitive antagonists for mGlu 5 receptors, such as MPEP, represents another novel approach to treating CNS disorders, and are useful pharmacological tools for studying mGlu 5 receptor functions in animal models.
CAS PubMed Google Scholar
- Tatarczynska, E., Klodzinska, A., Kroczka, B., Chojnacka-Wojcik, E. & Pilc, A. The antianxiety-like effects of antagonists of group I and agonists of group II and III metabotropic glutamate receptors after intrahippocampal administration. Psychopharmacology (Berl). 158, 94–99 (2001).
CAS PubMed Google Scholar
- Spooren, W. P., Gasparini, F., Bergmann, R. & Kuhn, R. Effects of the prototypical mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine on rotarod, locomotor activity and rotational responses in unilateral 6-OHDA-lesioned rats. Eur. J. Pharmacol. 406, 403–410 (2000).
CAS PubMed Google Scholar
- Tatarczynska, E. et al. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br. J. Pharmacol. 132, 1423–1430 (2001).
CAS PubMed PubMed Central Google Scholar
- Spooren, W. P. et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J. Pharmacol. Exp. Ther. 295, 1267–1275 (2000).
CAS PubMed Google Scholar
- Spooren, W. P., Schoeffter, P., Gasparini, F., Kuhn, R. & Gentsch, C. Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608). Eur. J. Pharmacol. 435, 161–170 (2002).
CAS PubMed Google Scholar
- Johnson, M. P., Kelly, G. & Chamberlain, M. Changes in rat serum corticosterone after treatment with metabotropic glutamate receptor agonists or antagonists. J. Neuroendocrinol. 13, 670–677 (2001).
CAS PubMed Google Scholar
- Brown, M. R. et al. Corticotropin-releasing factor: Effects on the sympathetic nervous system and oxygen consumption. Life Sci. 30, 207–210 (1982).
CAS PubMed Google Scholar
- Riedel, G., Casabona, G., Platt, B., Macphail, E. M. & Nicoletti, F. Fear conditioning-induced time- and subregion-specific increase in expression of mGlu5 receptor protein in rat hippocampus. Neuropharmacology 39, 1943–1951 (2000).
CAS PubMed Google Scholar
- Schulz, B. et al. The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in rats. Neuropharmacology 41, 1–7 (2001).
CAS PubMed Google Scholar
- Rolls, E. T. A theory of hippocampal function in memory. Hippocampus 6, 601–620 (1996).
CAS PubMed Google Scholar
- Rodrigues, S. M., Bauer, E. P., Farb, C. R., Schafe, G. E. & LeDoux, J. E. The group I metabotropic glutamate receptor mGluR5 is required for fear memory formation and long-term potentiation in the lateral amygdala. J. Neurosci. 22, 5219–5229 (2002).
CAS PubMed PubMed Central Google Scholar
- Bliss, T. V. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. Paris 232, 331–356 (1973).
CAS Google Scholar
- Bear, M. F. & Malenka, R. C. Synaptic plasticity: LTP and LTD. Curr. Opin. Neurobiol. 4, 389–399 (1994).
CAS PubMed Google Scholar
- Izumi, Y., Clifford, D. B. & Zorumski, C. F. 2-Amino-3-phosphonopropionate blocks the induction and maintenance of long-term potentiation in rat hippocampal slices. Neurosci. Lett. 122, 187–190 (1991).
CAS PubMed Google Scholar
- Behnisch, T. & Reymann, K. G. Co-activation of metabotropic glutamate and _N_-methyl-D-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons. Neuroscience 54, 37–47 (1993).
CAS PubMed Google Scholar
- Riedel, G., Casabona, G. & Reymann, K. G. Inhibition of long-term potentiation in the dentate gyrus of freely moving rats by the metabotropic glutamate receptor antagonist MCPG. J. Neurosci. 15, 87–98 (1995).
CAS PubMed PubMed Central Google Scholar
- Wang, J. & Johnson, K. M. Regulation of striatal cyclic-3′,5′-adenosine monophosphate accumulation and GABA release by glutamate metabotropic and dopamine D1 receptors. J. Pharmacol. Exp. Ther. 275, 877–884 (1995).
CAS PubMed Google Scholar
- Wilsch, V. W., Behnisch, T., Jager, T., Reymann, K. G. & Balschun, D. When are class I metabotropic glutamate receptors necessary for long-term potentiation? J. Neurosci. 18, 6071–6080 (1998).
CAS PubMed PubMed Central Google Scholar
- Ugolini, A., Corsi, M. & Bordi, F. Potentiation of NMDA and AMPA responses by the specific mGluR5 agonist CHPG in spinal cord motoneurons. Neuropharmacology 38, 1569–1576 (1999).
CAS PubMed Google Scholar
- Nielsen, K. S., Macphail, E. M. & Riedel, G. Class I mGlu receptor antagonist 1-aminoindan-1,5-dicarboxylic acid blocks contextual but not cue conditioning in rats. Eur. J. Pharmacol. 326, 105–108 (1997).
CAS PubMed Google Scholar
- Ohno, M. & Watanabe, S. Enhanced _N_-methyl-D-aspartate function reverses working memory failure induced by blockade of group I metabotropic glutamate receptors in the rat hippocampus. Neurosci. Lett. 240, 37–40 (1998).
CAS PubMed Google Scholar
- Semyanov, A. & Kullmann, D. M. Modulation of GABAergic signaling among interneurons by metabotropic glutamate receptors. Neuron 25, 663–672 (2000).
CAS PubMed Google Scholar
- Schrader, L. A. & Tasker, J. G. Modulation of multiple potassium currents by metabotropic glutamate receptors in neurons of the hypothalamic supraoptic nucleus. J. Neurophysiol. 78, 3428–3237 (1997).
CAS PubMed Google Scholar
- Schrader, L. A. & Tasker, J. G. Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons. J. Neurophysiol. 77, 527–536 (1997).
CAS PubMed Google Scholar
- Tatarczynska, E. et al. Anxiolytic- and antidepressant-like effects of group III metabotropic glutamate agonist (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I) in rats. Pol. J. Pharmacol. 54, 707–710 (2002).
CAS PubMed Google Scholar
- Chojnacka-Wojcik, E., Tatarczynska, E. & Pilc, A. Anxiolytic-like effects of metabotropic glutamate antagonist (RS)-α-methylserine-_O_-phosphate in rats. Pol. J. Pharmacol. 48, 507–509 (1996).
CAS PubMed Google Scholar
- Masugi, M. et al. Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion. J. Neurosci. 19, 955–963 (1999).
CAS PubMed PubMed Central Google Scholar
- Cryan, J. F. et al. Antidepressant and anxiolytic-like effects in mice lacking the group III metabotropic glutamate receptor mGluR7 . Eur. J. Neurosci. 17, 2409–2417 (2003).
PubMed Google Scholar
- Linden, A. M. et al. Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor. Neuropharmacology 43, 251–259 (2002). Group III mGlu receptors such as mGlu 8 might also be involved in the processing of stress responses in animals and might therefore also be interesting new drug targets for anxiety.
CAS PubMed Google Scholar
- Belzung, C. & Griebel, G. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav. Brain Res. 125, 141–149 (2001).
CAS PubMed Google Scholar
- Kilbride, J., Huang, L. Q., Rowan, M. J. & Anwyl, R. Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV. Eur. J. Pharmacol. 356, 149–157 (1998).
CAS PubMed Google Scholar
- Marek, G. J., Wright, R. A., Schoepp, D. D., Monn, J. A. & Aghajanian, G. K. Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex. J. Pharmacol. Exp. Ther. 292, 76–87 (2000). The distribution of mGlu 2/3 -binding sites in the rat prefrontal cortex overlaps with the expression of 5-HT 2A (serotonin) receptors in that region, and at the cellular level the actions of mGlu 2/3 receptor agonists and 5-HT 2A receptor antagonists both result in suppression of thalmocortical glutamate release. The pharmacological actions in certain models of psychosis and anxiety for these two classes of agents might therefore be through this common mechamism.
CAS PubMed Google Scholar
- Neugebauer, V., Chen, P. S. & Willis, W. D. Groups II and III metabotropic glutamate receptors differentially modulate brief and prolonged nociception in primate STT cells. J. Neurophysiol. 84, 2998–3009 (2000).
CAS PubMed Google Scholar
- Tizzano, J. P., Griffey, K. I. & Schoepp, D. D. The anxiolytic action of mGlu2/3 receptor agonist, LY354740, in the fear-potentiated startle model in rats is mechanistically distinct from diazepam. Pharmacol. Biochem. Behav. 73, 367–374 (2002). Both diazepam and LY354740 reduced fear expression in fear-conditioned rats using fear-potentiated startle as a readout of behaviour. However, systemically administered LY354740, unlike diazepam, did not prevent the development of fear-learning in this model. These data indicate that the applications of LY354740 across anxiety disorders might be different from the benzodiazepines.
CAS PubMed Google Scholar
- Linden, A. M., Bergeron, M., Baez, M. & Schoepp, D. D. Systemic administration of the potent mGlu8 receptor agonist (S)-3,4-DCPG induces c-Fos in stress-related brain regions in wild-type, but not mGlu8 receptor knockout mice. Neuropharmacology 45, 473–483 (2003).
CAS PubMed Google Scholar
- Walker, D. L., Rattiner, L. M. & Davis, M. Group II metabotropic glutamate receptors within the amygdala regulate fear as assessed with potentiated startle in rats. Behav. Neurosci. 116, 1075–1083 (2002).
CAS PubMed Google Scholar
- Grillon, C., Cordova, J., Levine, L. R. & Morgan, C. A. Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology (Berl). 168, 446–454 (2003). In humans, as in rats, LY354740 blocked the expression of fear-potentiated startle, without evidence of CNS depression caused by drugs such as the benzodiazepines. This shows that fear-potentiated startle can be used to assess or validate certain atypical anxiolytic agents across animal and human species.
CAS PubMed Google Scholar
- Klodzinska, A. et al. Potential anti-anxiety, anti-addictive effects of LY 354740, a selective group II glutamate metabotropic receptors agonist in animal models. Neuropharmacology 38, 1831–1839 (1999).
CAS PubMed Google Scholar
- Benvenga, M. J., Overshiner, C. D., Monn, J. A. & Leander, J. D. Disinhibitory effects of LY354740, a new mGluR2 agonist, on behaviors suppressed by electric shock, in rats and pigeons. Drug Dev. Res. 47, 37–44 (1999).
CAS Google Scholar
- Moore, N. A., Rees, G. & Monn, J. A. Effects of the group II metabotropic glutamate receptor agonist, LY354740 on schedule-controlled behaviour in rats. Behav. Pharmacol. 10, 319–325 (1999).
CAS PubMed Google Scholar
- Swanson, C. J., Perry, K. W. & Schoepp, D. D. The mGlu2/3 receptor agonist, LY354740, blocks immobilization-induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex. J. Neurochem. 88, 194–202 (2004). Stress responses that lead to enhanced release of brain monoamines can be suppressed by mGlu 2/3 receptor activation without effects on basal levels of these neurotransmitters.
CAS PubMed Google Scholar
- Schoepp, D. D. Case study: utility of metabotropic glutamate agonists in psychiatric illness. 5th World Congress on Stress. Abs 120 (2004).
- Yamanoi, K. & Ohfune, Y. Synthesis of trans and cis-α-(carboxycyclopropyl)glycines. Novel neuroinhibitory amino acids as L-glutamate analogue. Tetrahedron Lett. 29, 1181–4 (1988).
CAS Google Scholar
- Shimamoto, K., Ishida, M., Shinozaki, H. & Ohfune, Y. Synthesis of four diastereomeric L-2-carboxycyclopropy1) glycines. Conformationally constrained L-glutamate analogues. J. Org. Chem. 56, 4167–4176 (1991).
CAS Google Scholar
- Monn, J. A. et al. Synthesis of the four isomers of 4-aminopyrrolidine-2,4-dicarboxylate: identification of a potent, highly selective, and systemically-active agonist for metabotropic glutamate receptors negatively coupled to adenylate cyclase. J. Med. Chem. 39, 2990–3000 (1996).
CAS PubMed Google Scholar
- Acher, F. C. et al. Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes. J. Med. Chem. 40, 3119–3129 (1997).
CAS PubMed Google Scholar
- Kozikowski, A. P. et al. Synthesis and metabotropic glutamate receptor activity of a 2-aminobicyclo[3.2.0] heptane-2,5-dicarboxylic acid, a molecule possessing an extended glutamate conformation. Bioorg. Med. Chem. Lett. 8, 925–930 (1998).
CAS PubMed Google Scholar
- Monn, J. A. et al. Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors. J. Med. Chem. 42, 1027–1040 (1999).
CAS PubMed Google Scholar
- Schoepp, D. D. et al. LY354740 is a potent and highly selective group II metabotropic glutamate receptor agonist in cells expressing human glutamate receptors. Neuropharmacology 36, 1–11 (1997). LY354740 is a potent agonist for recombinant human mGlu 2/3 receptors and selectively activates endogenous brain rat mGlu 2/3 receptors in a stereoselective manner.
CAS PubMed Google Scholar
- Malherbe, P. et al. Identification of essential residues involved in the glutamate binding pocket of the group II metabotropic glutamate receptor. Mol. Pharmacol. 60, 944–954 (2001).
CAS PubMed Google Scholar
- Kunishima, N. et al. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407, 971–977 (2000).
CAS PubMed Google Scholar
- Varney, M. A. & Suto, C. M. Discovery of subtype-selective metabotropic glutamate receptor ligands using functional HTS assays. Drug Discov. Today 1, 20–26 (2000).
CAS Google Scholar
- Varney, M. A. et al. SIB-1757 and SIB-1893: selective, noncompetitive antagonists of metabotropic glutamate receptor type 5. J. Pharmacol. Exp. Ther. 290, 170–181 (1999). The use of high-throughput screening with functional mGlu receptor readouts led to novel subtype-selective and non-competitive mGlu 5 receptor antagonists.
CAS PubMed Google Scholar
- Pagano, A. et al. The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyimino-cyclopropan[b]chromen-1a-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of group I metabotropic glutamate receptors. J. Biol. Chem. 275, 33750–33758 (2000).
CAS PubMed Google Scholar
- Malherbe, P. et al. Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)–pyridine. Mol. Pharmacol. 64, 823–832 (2003).
CAS PubMed Google Scholar
- Linden, A. -M., Baez, M., Shannon, H., Bergerm, M. & Schoepp, D. D. The anxiolytic-like activity of LY354580 is absent in mGlu2 and mGlu3 knockout mice. Psychopharmacol. (in the press).