Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats.
Glutamatergic abnormalities have been associated with several psychiatric disorders, including schizophrenia and addiction. Group II metabotropic glutamate receptors were targeted to normalize glutamatergic disruptions associated with an animal model of schizophrenia, the phencyclidine model. An agonist of this group of receptors, at a dose that was without effects on spontaneous activity and corticolimbic dopamine neurotransmission, attenuated the disruptive effects of phencyclidine on working memory, stereotypy, locomotion, and cortical glutamate efflux. This behavioral reversal occurred in spite of sustained dopamine hyperactivity. Thus, targeting this group of receptors may present a nondopaminergic therapeutic strategy for treatment of psychiatric disorders.
Department of Psychiatry, Yale University School of Medicine, Veterans Administration Medical Center 116A/2, West Haven, CT 06516, USA.
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B
Moghaddam
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BW
Adams
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D018698:Glutamic Acid; D010622:Phencyclidine; C104753:eglumetad; D004298:Dopamine