Modulation of glycine sites enhances social memory in rats using PQQ combined with d-serine

- PQQ combined with d-serine can improve MK-801-induced social memory impairment.
- The co-agonist NMDA receptor, by activating glycine sites, can enhance social memory in normal rats.
- PQQ stimulates glycine modulatory sites by indirect antagonizing via removing glycine from the synaptic cleft.
- PQQ binding the unsaturated sites with d-serine in the brain stimulates glycine modulatory sites.

The aim of study was to investigate the effects of pyrroloquinoline quinone (PQQ) combined with d-serine on the modulation of glycine sites in the brain of rats using social recognition test. Rats were divided into seven groups (n = 10) and given repeated intraperitoneal (ip) injections of saline, MK-801 (0.5 mg/kg), clozapine (1 mg/kg), haloperidol (0.1 mg/kg), d-serine (0.8 g/kg), PQQ (2.0 μg/kg), or d-serine (0.4 g/kg) combined with PQQ (1.0 μg/kg) for seven days. A social recognition test, including assessment of time-dependent memory impairment, was performed. A non-competitive NMDA receptor antagonist, MK-801, significantly impaired social memory, and this impairment was significantly repaired with an atypical antipsychotic (clozapine) but not with a typical antipsychotic (haloperidol). Likewise, d-serine combined with PQQ significantly improved MK-801-disrupted cognition in naïve rats, whereas haloperidol was ineffective. The present results show that the co-agonist NMDA receptor treated with PQQ and d-serine enhances social memory and may be an effective approach for treating the cognitive dysfunction observed in schizophrenic patients. PQQ stimulates glycine modulatory sites by which it may antagonize indirectly by removing glycine from the synaptic cleft or by binding the unsaturated site with d-serine in the brain, providing the insights into future research of central nervous system and drug discovery.