Effects of the selective kainate receptor antagonist ACET on altered sensorimotor gating in a genetic model of reduced NMDA receptor function
| Autor: | Gary E. Duncan, Beverly H. Koller, Sheryl S. Moy |
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| Rok vydání: | 2012 |
| Předmět: |
Agonist
Kainic acid medicine.drug_class Nerve Tissue Proteins Kainate receptor Pharmacology Receptors N-Methyl-D-Aspartate Article Mice chemistry.chemical_compound Receptors Kainic Acid Genetic model medicine Animals Uracil Receptor Molecular Biology Alanine biology General Neuroscience Antagonist GRIN1 Isoxazoles Disease Models Animal nervous system chemistry Gene Knockdown Techniques Schizophrenia biology.protein NMDA receptor Neurology (clinical) Propionates Carrier Proteins Antipsychotic Agents Developmental Biology |
| Zdroj: | Brain Research. 1443:98-105 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2012.01.009 |
| Popis: | The pathophysiology of schizophrenia may involve reduced NMDA receptor function. Accordingly, experimental models of NMDA receptor hypofunction may be useful for testing potential new antipsychotic agents and for characterizing neurobiological abnormalities relevant to schizophrenia. We demonstrated previously that mice under-expressing the NR1 subunit of the NMDA receptor show supersensitive behavioral responses to kainic acid and that a kainate receptor antagonist normalized altered behaviors in the mutant mice (NR1(neo/neo)). The present work examined effects of another selective kainate receptor antagonist, (S)-1-(2-Amino-2-carboxyethyl)-3-(2-carboxy-5-phenylthiophene-3-yl-methylpyrimidine-2,4-dione (ACET), on altered behavioral phenotypes in the genetic model of NMDA receptor hypofunction. ACET, at a dose of 15 mg/kg, partially reversed the deficits in prepulse inhibition produced by the mutation. The 15 mg/kg dose of ACET was also effective in reversing behavioral effects of the selective kainate agonist ATPA. However, ACET did not significantly reduce the increased locomotor activity and rearing behavior observed in the NR1(neo/neo) mice. These findings show that a highly selective kainate receptor antagonist can affect the deficits in sensorimotor gating in the NR1(neo/neo) mice. The results also provide further support for the idea that selective kainate receptor antagonists could be novel therapeutic candidates for schizophrenia. |
| Databáze: | OpenAIRE |
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