Mar 25, 2011

Interaction of mGlu2/3 agonism with clozapine and lurasidone to restore novel object recognition in subchronic phencyclidine-treated rats

Masakuni HoriguchiHerbert Y Meltzer


Subchronic administration to rodents of the N-methyl-D-aspartate non-competitive antagonist, phencyclidine (PCP), impairs novel object recognition (NOR). Atypical antipsychotic drugs (APDs) reverse the effects of subchronic PCP on NOR. The effect of metabotropic glutamate₂/₃ receptor (mGlu₂/₃) agonists upon NOR is unknown. We tested the hypotheses that the mGlu₂/₃ agonist, LY379268, by itself, or in combination with APDs or pimavanserin, a 5-HT(2A) inverse agonist, would reverse the deficit in NOR induced by subchronic treatment with PCP (2 mg/kg, b.i.d., for 7 days). The mGlu₂/₃ agonist LY379268 (1 or 3 mg/kg) did not attenuate the PCP-induced NOR deficit. However, together with sub-effective dose of the atypical APDs, clozapine (0.1 mg/kg) or lurasidone (0.03 mg/kg), but not the typical APD, haloperidol (0.1 mg/kg), or pimavanserin (3 mg/kg), LY379268, 1 mg/kg, significantly reversed the PCP-induced NOR deficit. Moreover, the effect of clozapine was blocked by the mGlu₂/₃ antagonist, LY341495 (1 mg/kg). These results indicate that mGlu₂/₃ agonism can potentiate the ability of atypical, but not typical APDs, to ameliorate the effect of subchronic PCP on NOR, that mGlu₂/₃ agonism may contribute to the ability of atypical APDs t...Continue Reading

Mentioned in this Paper

Metabotropic glutamate receptors type 3
Antipsychotic Effect
Atypical Antipsychotic [EPC]
Receptor, Serotonin,5-HT2A
Neurologic Manifestations
Assay OF Haloperidol
Phencyclidine Hydrobromide
LY 379268

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