Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats

An agonist of group II metabotropic glutamate receptors, at a dose that did not affect spontaneous activity or corticolimbic dopamine neurotransmission, reduced the disruptive effects of phencyclidine on working memory, stereotypy, locomotion, and cortical glutamate efflux in an animal model of schizophrenia. This behavioral reversal occurred despite sustained dopamine hyperactivity, suggesting that targeting these receptors may offer a nondopaminergic therapeutic strategy for psychiatric disorders such as schizophrenia and addiction.

Study at a glance

Abstract

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.