Antagonism of phencyclidine-induced hyperactivity by glycine in mice

Abstract

We tested the effect of glycine on phencyclidine (PCP)-induced hyperactivity in mice. Glycine antagonized the locomotor stimulating effect of PCP. Correlation was found between the degree of antagonistic effect and the size of the increase in glycine in the brain. The antagonism is not due to changes in uptake, since the elevation of glycine in plasma and brain had no effect on the cerebral uptake of PCP. This pharmacological action of glycine appears to be a central effect, but some peripheral effect can not be excluded. Since glycine is not toxic at levels needed for PCP antagonism, it could be considered for ameliorating PCP psychosis. The locomotor stimulating effect of PCP is strain dependent in mouse. Some strains are responsive, such as BALB/cBy and CXBK, and some are unresponsive, such as C57BL/6 and CXBH.

NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia

“…This is a well established point and consistent with this direct effect, allosteric modifications of the NMDA receptor can reverse some actions of PCP in animal models. 53 Thus, we do not question the direct effect, just its selectivity at relevant doses. Third, while we have shown a direct effect on the dopamine D 2 and serotonin 5-HT 2 receptors in vitro, it is yet to be determined which of the behavioural effects of these challenges are attributable to these direct effects.…”

Inhibition of System A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine: implications for mechanisms of action

“…Initial studies were performed with glycyldodecylamide (GDA), a compound that reversed behavioral effects of the NMDA antagonist PCP in rodents, 67,68 which was subsequently shown to inhibit glycine uptake in synaptosomes. 69,70 More recent studies have been performed using NFPS or other high-affinity glycine transport inhibitors such as Org 24598.…”

The Family of Na+/Cl− Neurotransmitter Transporters

“…In contrast, pheneyclidine (PCP) induces a schizophrenia-like psychotic state by blocking the NMDA receptor (Javitt et al, 1994(Javitt et al, , 1996. Experimental evidence suggests that elevation of glycine concentrations in the brain reverses PCP-indueed behaviors in rodents (Toth and Lajtha, 1986). Moreover, a significant improvement in negative symptoms was observed when a g!yeine transporter inhibitor glycyldodecylamide was given to PCP-treated animals (Javitt et al, 1997).…”