Abstract
Previous studies suggest that metabotropic glutamate 2/3 receptors are involved in psychiatric disorders. In this study, we examined the effects of the selective metabotropic glutamate 2/3 (mGlu2/3) receptor agonist MGS0028 on behavioral abnormalities in mice lacking the pituitary adenylate cyclase-activating polypeptide (PACAP), an experimental model of psychiatric disorders such as schizophrenia and attention-deficit/hyperactivity disorder. We found that PACAP-deficient mice showed impairments in the novel object recognition test and these impairments were improved by MGS0028 (0.1 mg/kg). Similarly, MGS0028 improved hyperactivity and jumping behaviors, but did not reverse increased immobility times in the forced swim test in PACAP-deficient mice. These results suggest that MGS0028 may be a potential, novel treatment for psychiatric disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antipsychotic Agents / therapeutic use*
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Attention Deficit Disorder with Hyperactivity / drug therapy*
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Attention Deficit Disorder with Hyperactivity / metabolism
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Behavior, Animal / drug effects
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Brain / drug effects
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Brain / metabolism
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Bridged Bicyclo Compounds / therapeutic use*
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Dicarboxylic Acids / therapeutic use*
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Disease Models, Animal
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Male
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Memory Disorders / drug therapy*
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Memory Disorders / metabolism
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Mice
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Mice, Mutant Strains
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Molecular Targeted Therapy
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Nerve Tissue Proteins / agonists
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / metabolism
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Nootropic Agents / therapeutic use*
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Pituitary Adenylate Cyclase-Activating Polypeptide / genetics
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Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism*
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Receptors, Metabotropic Glutamate / agonists*
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Receptors, Metabotropic Glutamate / metabolism
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Recognition, Psychology / drug effects
Substances
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Adcyap1 protein, mouse
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Antipsychotic Agents
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Bridged Bicyclo Compounds
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Dicarboxylic Acids
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Nerve Tissue Proteins
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Nootropic Agents
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor 2
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metabotropic glutamate receptor 3
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MGS 0028