Stimulation of metabotropic glutamate (mGlu) 2 receptor and blockade of mGlu1 receptor improve social memory impairment elicited by MK-801 in rats

Glutamatergic dysfunction has been implicated in psychiatric disorders such as schizophrenia. both the stimulation of the metabotropic glutamate (mglu) 2/3 receptor and the blockade of the mglu1 receptor have been shown to be effective in a number of animal models of schizophrenia. however,the efficacy for social cognition,which is poorly managed by current medication,has not been fully addressed. the present study evaluated the effects of an mglu2/3-receptor agonist and an mglu1-receptor antagonist on social memory impairment in rats. pretreatment with an mglu2/3-receptor agonist,(-)-2-oxa-4-aminobicyclo[3.1.0] hexane-4,6-dicarboxylate (ly379268),or an mglu1-receptor antagonist,(3,4-dihydro-2h-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone (jnj16259685),improved social memory impairment induced by 5r,10s-(+)-5-methyl- 10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (mk-801) without affecting the social interactions. in addition,the intraperitoneal administration of an mglu2-receptor potentiator,3′-[[(2-cyclopentyl-2,3- dihydro-6,7-dimethyl-1-oxo-1h-inden-5-yl)oxy]methyl]-[1,1′-biphenyl] -4-carboxylic acid (bina),also improved the mk-801-induced impairment of social memory,which was blocked by pretreatment with an mglu2/3-receptor antagonist,(2s)-2-amino-2-[(1s,2s)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (ly341495). these findings indicate that both the stimulation of the mglu2 receptor and the inhibition of an mglu1 receptor improve social memory impairment elicited by mk-801,and both manipulations could be effective approaches for the treatment of certain cognitive dysfunctions observed in schizophrenic patients. © the japanese pharmacological society.