Assessment of NMDA receptor activation in vivo by Fos induction after challenge with the direct NMDA agonist (tetrazol-5-yl)glycine: effects of clozapine and haloperidol
| Autor: | Sheryl S. Moy, Gary E. Duncan, Beverly H. Koller, Joseph Farrington, Ken Inada |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
N-Methylaspartate Glycine Tetrazoles Mice Transgenic Pharmacology Hippocampal formation Receptors Metabotropic Glutamate Hippocampus Receptors N-Methyl-D-Aspartate Mice Dopamine Dopamine receptor D2 Haloperidol medicine Animals Receptor Clozapine Biological Psychiatry Mice Knockout Chemistry Glutamate receptor Mice Inbred C57BL Psychiatry and Mental health Neurology Mice Inbred DBA NMDA receptor Neurology (clinical) Proto-Oncogene Proteins c-fos medicine.drug |
| Zdroj: | Journal of Neural Transmission. 114:899-908 |
| ISSN: | 1435-1463 0300-9564 |
| DOI: | 10.1007/s00702-007-0628-5 |
| Popis: | Induction of Fos protein by the potent and direct NMDA agonist (tetrazol-5-yl)glycine (TZG) was examined in mice. Effects of antipsychotic drugs were assessed on this in vivo index of NMDA receptor activation. TZG induced the expression of Fos in a neuroanatomically selective manner, with the hippocampal formation showing the most robust response. In mice genetically altered to express low levels of the NR1 subunit of the NMDA receptor, TZG-induced Fos was reduced markedly in comparison to the wild type controls. TZG-induced Fos was also blocked by the selective NMDA antagonist MK-801. Pretreatment of mice with clozapine (3 and 10 mg/kg) reduced TZG-induced Fos in the hippocampal formation but not in other brain regions. Haloperidol at a dose of 0.5 mg/kg did not antagonize TZG induced Fos in any region. Haloperidol at a dose of 1.0 mg/kg did attenuate the induction of Fos by TZG in the hippocampus but not in other brain regions. The relatively high dose (1 mg/kg) of haloperidol required to block effects of TZG suggests that this action may not be related to the D(2) dopamine receptor-blocking properties, since maximal D(2) receptor blockade was probably achieved by the 0.5 mg/kg dose of haloperidol. The antidepressant drug imipramine (10 or 20 mg/kg) did not antagonize TZG induced Fos in any brain region. The data suggest that clozapine can reduce excessive activation of NMDA receptors by TZG administration in vivo at doses relevant to the drugs' actions in rodent models of antipsychotic activity. Whether or not this action of clozapine contributes to its therapeutic properties will require further study. |
| Databáze: | OpenAIRE |
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