NMDA receptor antagonists change behavioral activity of rats treated with (S)-4CPG.

The effect of (S)-4CPG [(S)-4-carboxyphenylglycine] (25, 50, 100 nmol icv) and the effect of AP-7 (5 nmol icv) or MK-801 (5 nmol icv) on the processes of acquisition, consolidation of conditioned reflexes and locomotor activity were tested in rats. Neither AP-7, MK-801 nor (S)-4CPG given alone changed locomotor activity. MK-801 significantly increased the effects of (S)-4CPG: on crossings at all applied doses, on rearings at 100 nmol, and on bar approaches at 50 nmol of (S)-4CPG. AP-7 enhanced the effects of 50 and 100 nmols of (S)-4CPG on crossings, 100 nmol of (S)-4CPG on rearings in the open field test. Neither AP-7, MK-801 nor (S)-4CPG at doses of 50 and 100 nmols influenced acquisition, but (S)-4CPG given alone at a dose of 25 nmol impaired acquisition. MK-801 impaired the action of 50 and 100 nmols of (S)-4CPG on acquisition. AP-7 only at a dose of 100 nmol inhibited (S)-4CPG-induced acquisition. Neither AP-7, MK-801 nor (S)-4CPG given alone changed consolidation in passive avoidance situation while co-administration of AP-7 and (S)-4CPG at the doses of 50 and 100 nmols, affected this process. The obtained results support our hypothesis concerning the co-operation between group I mGluRs and NMDA receptors in some behavioral tests and the modulating effect of group I mGluRs antagonist on central action of NMDA receptor antagonists.