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Effects of a metabotropic glutamate receptor group II agonist LY354740 in animal models of positive schizophrenia symptoms and cognition
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Schlumberger, Chantal, Schäfer, Daniela, Barberi, Caroline, Morè, Lorenzo, Nagel, Jens, Pietraszek, Małgorzata, Schmidt, Werner J. and Danysz, Wojciech (2009) Effects of a metabotropic glutamate receptor group II agonist LY354740 in animal models of positive schizophrenia symptoms and cognition. Behavioural Pharmacology , 20 (1). pp. 56-66. doi:10.1097/FBP.0b013e3283242f57 ISSN 1473-5849.
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Official URL: http://dx.doi.org/10.1097/FBP.0b013e3283242f57
Abstract
It has been proposed that activation of metabotropic glutamate receptor subtype 2/3 (mGluR2/3) may induce both antipsychotic and anxiolytic effects. The aim of this study was to evaluate further the effect of the mGluR2/3 agonist, LY354740 [(+)-2-aminobicyclo(3.1.0)hexane-2,6-dicarboxylate monohydrate] in animal models relevant to both psychotic and cognitive impairment in schizophrenia. The elevated plus maze was used to select the doses for further experiments, LY354740 induced anxiolytic-like effects at doses of 3 and 10 mg/kg but not 1 mg/kg. At a dose of 10 mg/kg. LY354740 attenuated phencyclidine (PCP)-induced locomotor activity. Administered alone, it had no effect on horizontal activity, but at doses of 3 and 10 mg/kg, slightly decreased vertical activity (rearings). LY354740 (1–10 mg/kg intraperitoneally) affected neither prepulse inhibition in normal rats nor reversed the disruption of prepulse inhibition produced by PCP (2 mg/kg subcutaneously). Moreover, LY354740 (3–10 mg/kg) did not modify PCP-induced working memory deficits assessed in a spontaneous alternation task and had no effect on PCP-evoked amnesia in the passive avoidance test. LY354740 alone (3 and 10 mg/kg) induced working memory deficits, but had no effect on acquisition of passive avoidance. In conclusion, LY354740 was effective in models for anxiety and positive symptoms of schizophrenia but not in models for sensorimotor gating and cognitive impairment.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Schizophrenia -- Research, Glutamic acid, Antipsychotic drugs | ||||
| Journal or Publication Title: | Behavioural Pharmacology | ||||
| Publisher: | Lippincott Williams & Wilkins | ||||
| ISSN: | 1473-5849 | ||||
| Official Date: | 2009 | ||||
| Dates: |
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| Volume: | 20 | ||||
| Number: | 1 | ||||
| Page Range: | pp. 56-66 | ||||
| DOI: | 10.1097/FBP.0b013e3283242f57 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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