Lamotrigine reduced the overflow of dopamine and serotonin in the medial prefrontal cortex of awake rats after administration of phencyclidine (PCP), a drug that mimics psychotic-like behavior. The effect on noradrenaline was not statistically significant. Lamotrigine did not affect PCP-induced hyperactivity, suggesting different brain circuits are involved in these processes. The findings support lamotrigine's potential as an add-on treatment for schizophrenia by preventing neurochemical changes linked to psychotomimetic effects.
NMDA receptor antagonists like ketamine and phencyclidine produce psychosis-like symptoms in healthy people and those with schizophrenia, making them useful as models for developing new schizophrenia treatments. This review examines whether these models have predictive validity based on results from recent clinical trials of novel treatments. It also assesses how different hypotheses about the drugs' psychotomimetic effects hold up against trial data. The authors discuss limitations of the models and suggest that incorporating translational markers could improve understanding of how these models relate to schizophrenia.