title: Stimulation of the metabotropic glutamate (mGlu) 2 receptor attenuates the MK-801-induced increase in the immobility time in the forced swimming test in rats.
abstract: BACKGROUND
  Negative symptoms of schizophrenia are poorly managed using the currently available antipsychotics. Previous studies indicate that agonists of the metabotropic glutamate (mGlu) 2/3 receptors may provide a novel approach for the treatment of schizophrenia. However, the effects of mGlu2/3 receptor agonists or mGlu2 receptor positive allosteric modulators have not yet been clearly elucidated in animal models of the negative symptoms of schizophrenia. Recently, we reported that the forced swimming test in rats treated with subchronic MK-801, an NMDA receptor antagonist, may be regarded as a useful test to evaluate the activities of drugs against the negative symptoms of schizophrenia.
  
  
  METHODS
  We evaluated the effects of LY379268, an mGlu2/3 receptor agonist, and BINA, an mGlu2 receptor positive allosteric modulator, on the hyperlocomotion induced by acute administration of MK-801 (0.15mg/kg, sc) and on the increase in the immobility time in the forced swimming test induced by subchronic treatment with MK-801 (0.5mg/kg, sc, twice a day for 7 days) in rats.
  
  
  RESULTS
  Both LY379268 (3mg/kg, sc) and BINA (100mg/kg, ip) attenuated the increase in the immobility time induced by subchronic treatment with MK-801 at the same doses at which they attenuated the MK-801-induced increase in locomotor activity, but had no effect on the immobility time in saline-treated rats.
  
  
  CONCLUSIONS
  The present results suggest that stimulation of the mGlu2 receptor attenuates the increase in the immobility time in the forced swimming test elicited by subchronic administration of MK-801, and may be potentially useful for treatment of the negative symptoms of schizophrenia.
authors.affiliation: Pharmacology 1, Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawaura
authors.affiliation: Pharmacology 1, Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Karasawa
authors.affiliation: Pharmacology 1, Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., Saitama, Japan. Electronic address: h-hikichi@so.taisho.co.jp.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hikichi
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism*; D013550:Swimming / Q000502:physiology*
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D016291:Dizocilpine Maleate
keywords: Forced swimming test; MK-801; Schizophrenia; mGlu2 receptor positive allosteric modulator; mGlu2/3 receptor agonist