behavioral effects, providing proof of concept for ongoing treatment. Moreover, repeated dosing did not appear to induce tolerance to the effect on mGlu5 receptor density or phosphorylation of NMDA, NR1 (‘GluN1’) and NR2B (‘GluN2b’) receptor subunits in striatum, although tolerance was noted in the frontal cortex and in effects on sleep architecture. Finally, in a PET study in baboons [36▪], N-acetylcysteine treatment led to decreased binding of a radiotracer for the mGlu5 receptor, suggesting that N-acetylcysteine may lead to increased glutamate levels at the mGlu5 receptor and the NMDA receptor, possibly by exchange through the cystine-glutamate antiporter.
