Blockade of ventral midbrain NMDA receptors enhances brain stimulation reward: A preferential role for GluN2A subunits

R-CPP and PPPA produced a dose and time dependent decrease in reward threshold, an effect that was, at some doses and times after the injection, accompanied by an increase in maximum responses. These effects were not observed with Ro04-5595 over the range of doses tested. While previous studies suggest a role for glutamate in reward signaling, the present results show that VM glutamate exerts a tonic inhibition on the reward-relevant pathway. The selectivity of Ro04-5595 for NMDA receptors composed of GluN2B subunits and the higher affinity of R-CPP and PPPA for GluN2A suggest that the inhibition is mediated by receptors composed of GluN2A subunits.