The Selective mGlu5 Receptor Antagonist MTEP, Similar to NMDA Receptor Antagonists, Induces Social Isolation in Rats
| Autor: | Eliza Koros, Carmen Weiss, Frank Sams-Dodd, Gerald Birk, Holger Rosenbrock |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Pyridines medicine.drug_class Movement Receptor Metabotropic Glutamate 5 Pharmacology Receptors Metabotropic Glutamate Receptors N-Methyl-D-Aspartate Drug Administration Schedule Internal medicine Animals Medicine Interpersonal Relations Rats Wistar Phencyclidine Analysis of Variance Behavior Animal Dose-Response Relationship Drug business.industry Metabotropic glutamate receptor 5 Memantine Receptor antagonist Rats Thiazoles Psychiatry and Mental health Stereotypy (non-human) MTEP Metabotropic receptor Endocrinology Social Isolation NMDA receptor Stereotyped Behavior business Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Neuropsychopharmacology. 32:562-576 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/sj.npp.1301133 |
| Popis: | It has repeatedly been shown that uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can mimic certain aspects of positive and negative symptoms of schizophrenia in human volunteers and laboratory animals. The purpose of the present study was to expand these findings and to determine whether the selective metabotropic glutamate receptor subtype 5 (mGluR5) antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine), could induce similar effects in Wistar rats. First, MTEP (1.0-10.0 mg/kg; intraperitoneally) after acute and subchronic (daily for 5 days) administration as well as the uncompetitive antagonists of the NMDA receptor of either high affinity, phencyclidine (0.5-4.0 mg/kg; subcutaneously (s.c.)) and (+)-MK-801 (0.03-0.25 mg/kg; s.c.), or low-moderate affinity, ketamine (2.0-16.0 mg/kg; s.c.) and memantine (0.15-20.0 mg/kg; s.c.), following daily administration for 3 days were tested in the social interaction test to determine their ability to reproduce the negative and positive symptoms measured by social isolation and stereotyped behavior, respectively. Second, the compounds were tested in the motility test following acute administration to determine their ability to induce locomotor hyperactivity reflecting the positive symptoms. In line with previous findings, all examined NMDA receptor antagonists produced social interaction deficits, locomotor hyperactivity, and stereotypy except memantine. Notably, this study found that MTEP following both acute and subchronic administration dose-dependently induced social isolation, but did not cause either locomotor hyperactivity or stereotypy. These data demonstrate that social behavior deficits in rats can be caused by both the blockade of the NMDA receptor and the inhibition of mGluR5, whereas mGluR5 antagonists may not independently be able to mimic the positive symptoms. |
| Databáze: | OpenAIRE |
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