NMDA receptor antagonists acting at the glycine(B) site in rat models for antipsychotic-like activity

Several partial agonist and full antagonists acting at the glycine site of the NMDA receptors were tested for potential antipsychotic-like properties in rats. As models, amphetamine- and phencyclidine (PCP)-induced locomotor activation in the open field and PCP-induced impairment of prepulse inhibit ion of the acoustic startle response were employed. In the open field test, partial agonists, D-cycloserine failed to show any effect, aminocyclopropa ne carboxylic acid (ACPC) enhanced the action of PCP (but not that of amphe tamine) and R(+)HA-966 attenuated the locomotor activation produced by both amphetamine and PCP. Both full glycine, antagonists, L-701,324 and MRZ 2/5 76 attenuated the action of amphetamine and PCP but at the doses that also produce transient behavioural inhibition in naive animals. A competitive NM DA receptor antagonist CGP 39551 was ineffective. In the prepulse inhibitio n test neither L-701,324 nor MRZ 2/576 changed sensorimotor gating in naive animals nor attenuated the disrupting effects of PCP. The present data do not support antipsychotic profile of glycine, full antagonists. However, ps ychotomimetic potential of glycine, antagonists seems to be low.