The Potent, Selective mGlu2/3 Receptor Agonist LY379268 Increases Extracellular Levels of Dopamine, 3,4-Dihydroxyphenylacetic Acid, Homovanillic Acid, and 5-Hydroxyindole-3-Acetic Acid in the Medial Prefrontal Cortex of the Freely Moving Rat
| Autor: | Kenneth W. Perry, Jayne Cartmell, Craig R. Salhoff, Darryle D. Schoepp, James A. Monn |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Agonist medicine.medical_specialty 3 4-Dihydroxyphenylacetic acid medicine.drug_class Dopamine Prefrontal Cortex Receptors Metabotropic Glutamate Biochemistry Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine Excitatory Amino Acid Agonists medicine Animals Amino Acids Clozapine Homovanillic acid Dopaminergic Homovanillic Acid Hydroxyindoleacetic Acid Bridged Bicyclo Compounds Heterocyclic Receptor antagonist Rats Kinetics Endocrinology Metabotropic receptor Xanthenes nervous system chemistry Metabotropic glutamate receptor 3 4-Dihydroxyphenylacetic Acid Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Journal of Neurochemistry. 75:1147-1154 |
| ISSN: | 0022-3042 |
| Popis: | Previous work has shown that the potent, selective metabotropic glutamate mGlu2/3 receptor agonist LY379268 acts like the atypical antipsychotic clozapine in behavioral assays. To investigate further the potential antipsychotic actions of this agent, we examined the effects of LY379268 using microdialysis in awake, freely moving rats, on extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) in rat medial prefrontal cortex. Systemic LY379268 increased extracellular levels of dopamine, DOPAC, HVA, and 5-HIAA in a dose-dependent, somewhat delayed manner. LY379268 (3 mg/kg s.c.) increased levels of dopamine, DOPAC, HVA, and 5-HIAA to 168, 170, 169, and 151% of basal, respectively. Clozapine (10 mg/kg) also increased dopamine, DOPAC, and HVA levels, with increases of 255, 262, and 173%, respectively, but was without effect on extracellular 5-HIAA levels. The increases in DOPAC, HVA, and 5-HIAA levels by 3 mg/kg LY379268 were reversed by the selective mGlu2/3 receptor antagonist LY341495 (1 mg/kg). Furthermore, LY379268 (3 mg/kg)-evoked increases in DOPAC and HVA were partially blocked and the increase in 5-HIAA was completely blocked by local application of 3 μM tetrodotoxin. Therefore, we have demonstrated that mGlu2/3 receptor agonists activate dopaminergic and serotonergic brain pathways previously associated with the action of atypical antipsychotics such as clozapine and other psychiatric agents. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text