Group II mGlu Receptor Activation Suppresses Norepinephrine Release in the Ventral Hippocampus and Locomotor Responses to Acute Ketamine Challenge

Autor: Linda J. Bristow, Blake A. Rowe, Mark A. Varney, Jean-Michel Vernier, Lucia D Correa, Daniel S. Lorrain, Dana E. Rodriguez, Christopher Baccei, Jeffery J. Anderson, Una Campbell, Hervé Schaffhauser, Anthony B. Pinkerton
Rok vydání: 2003
Předmět:
Male
Time Factors
Microdialysis
Hippocampus
Pharmacology
Receptors
Metabotropic Glutamate
Rats
Sprague-Dawley
Norepinephrine
chemistry.chemical_compound
Excitatory Amino Acid Agonists
Drug Interactions
Amino Acids
Receptor
Neurotransmitter
Chromatography
High Pressure Liquid
6-Cyano-7-nitroquinoxaline-2
3-dione
Chemistry
Glutamate receptor
Psychiatry and Mental health
Area Under Curve
Ketamine
Agonist
Serotonin
medicine.drug_class
Glutamic Acid
Prefrontal Cortex
Hyperkinesis
In Vitro Techniques
Motor Activity
Sulfur Isotopes
medicine
Animals
Humans
Rats
Wistar
Analysis of Variance
Binding Sites
Dose-Response Relationship
Drug
Trifluoroethanol
Bridged Bicyclo Compounds
Heterocyclic
Rats
Disease Models
Animal
Metabotropic receptor
Xanthenes
Guanosine 5'-O-(3-Thiotriphosphate)
Metabotropic glutamate receptor
Schizophrenia
Excitatory Amino Acid Antagonists
Zdroj: Neuropsychopharmacology. 28:1622-1632
ISSN: 1740-634X
0893-133X
DOI: 10.1038/sj.npp.1300238
Popis: Group II mGlu receptor agonists (eg LY379268 and LY354740) have been shown to reverse many of the behavioral responses to PCP as well as glutamate release elicited by PCP and ketamine. In the present set of experiments, we used in vivo microdialysis to show that, in addition to reversing PCP- and ketamine-evoked glutamate release, group II mGlu receptor stimulation also prevents ketamine-evoked norepinephrine (NE) release. Pretreating animals with the mixed 2/3 metabotropic glutamate (mGlu2/3) receptor agonist LY379268 (0.3-10 mg/kg) dose-dependently inhibited ketamine (25 mg/kg)-evoked NE release in the ventral hippocampus (VHipp). Ketamine hyperactivity was also reduced in a similar dose range. Following our initial observation on NE release, we conducted a series of microinjection experiments to reveal that the inhibitory effects of LY379268 on VHipp NE release may be linked to glutamate transmission within the medial prefrontal cortex. Finally, we were able to mimic the inhibitory effects of LY379268 on ketamine-evoked NE release by using a novel mGlu2 receptor selective positive modulator. (+/-) 2,2,2-Trifluoroethyl [3-(1-methyl-butoxy)-phenyl]-pyridin-3-ylmethyl-sulfonamide (2,2,2-TEMPS, characterized through in vitro GTPgammaS binding) at a dose of 100 mg/kg significantly reduced the NE response. Together, these results demonstrate a novel means to suppress noradrenergic neurotransmission (ie by activating mGlu2 receptors) and may, therefore, have important implications for neuropsychiatric disorders in which aberrant activation of the noradrenergic system is thought to be involved.
Databáze: OpenAIRE
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