The glycine antagonist (+)-HA-966 injected into the nucleus accumbens stimulates locomotion in mice

Abstract

We have previously observed that NMDA antagonists injected into the ventral striatum cause locomotor stimulation in both normal and monoamine-depleted mice. Since glycine receptor activation is claimed to be a prerequisite for NMDA receptor channel opening, also a glycine site antagonist injected into the ventral striatum should cause behavioural activation. The present study was aimed at investigating whether this is the case. The glycine site antagonist (+)-HA-966, as well as its (-)-enantiomer, were injected bilaterally into the nucleus accumbens of normal, habituated mice. (+)-HA-966, but not (-)-HA-966, was found to stimulate locomotion. The stereoselective response suggests that the underlying mechanism involves the NMDA receptor-coupled glycine site. The present results support the notion that a glycine agonist might be of value in the treatment of schizophrenia, whereas a glycine antagonist should be expected to have psychotogenic effects.

Schizophrenia: From Dopamine to Glutamate and Back

“…Furthermore, we observed psychotomimetic actions of the glycine antagonist (+)-HA-966 following local administration into the nucleus accumbens of mice, results that are in consonance with the psychotogenic effects reported with D-cycloserine in man [37,38]. Interestingly, there is some evidence that the enhanced dopaminergic tone observed in the active psychotic phase of schizophrenia (see Introduction) is secondary to deficient glutamate transmission [39].…”