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.