Attenuation of specific PCP-evoked behaviors by the potent mGlu2/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine.
Psychopharmacology March 1, 2000 J Cartmell, J A Monn, D D Schoepp
A selective activator of metabotropic glutamate receptors (mGlu2/3), LY379268, reduces specific abnormal behaviors induced by the drug phencyclidine (PCP) in rats, similar to the antipsychotic clozapine. LY379268 and clozapine dose-dependently decreased PCP-evoked falling, turning, and back pedaling. At 30 minutes after PCP, 1 mg/kg LY379268 reduced falls by 89% and turns by 53%, while 1 mg/kg clozapine reduced turning by 70%. Low clozapine doses increased PCP-induced falls. Back pedaling was completely blocked by 1 mg/kg of either drug. However, clozapine's effects occurred only at doses that worsened PCP-evoked ataxia, whereas LY379268 did not. The findings suggest mGlu2/3 receptors selectively modulate certain PCP behaviors, supporting their potential as drug targets for schizophrenia.