It has been proposed that activation of
metabotropic glutamate receptor subtype 2/3 (
mGluR2/3) may induce both
antipsychotic and
anxiolytic effects. The aim of this study was to evaluate further the effect of the
mGluR2/3 agonist,
LY354740 [(+)-2-aminobicyclo(3.1.0)
hexane-2,6-dicarboxylate monohydrate] in animal models relevant to both psychotic and
cognitive impairment in
schizophrenia. The elevated plus maze was used to select the doses for further experiments,
LY354740 induced
anxiolytic-like effects at doses of 3 and 10 mg/kg but not 1 mg/kg. At a dose of 10 mg/kg.
LY354740 attenuated
phencyclidine (PCP)-induced locomotor activity. Administered alone, it had no effect on horizontal activity, but at doses of 3 and 10 mg/kg, slightly decreased vertical activity (rearings).
LY354740 (1-10 mg/kg intraperitoneally) affected neither prepulse inhibition in normal rats nor reversed the disruption of prepulse inhibition produced by PCP (2 mg/kg subcutaneously). Moreover,
LY354740 (3-10 mg/kg) did not modify PCP-induced working memory deficits assessed in a spontaneous alternation task and had no effect on PCP-evoked
amnesia in the passive avoidance test.
LY354740 alone (3 and 10 mg/kg) induced working memory deficits, but had no effect on acquisition of passive avoidance. In conclusion,
LY354740 was effective in models for anxiety and positive symptoms of
schizophrenia but not in models for sensorimotor gating and
cognitive impairment.