NMDA receptor-mediated modulation of dopamine neuro-transmission in the central nervous system

A deficiency in glutamateigic neurotransmission resulting in a disturbed balance between glutamatergic and dopaminergic systems in CNS has been implicated in pathophysiology of schizophrenia. In order to investigate the interaction between N-methyl D-aspartate (NMDA) and dopamine (DA) receptors in the CNS, we examined the effect of an NMDA receptor antagonist, 3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) on DA neurotransmission. Male Sprague Dawley rats cannulated bilaterally into the medial prefrontal cortex and injected with CPP and saline as control. Drug effects were evaluated in changes of behaviours associated with NMDA receptor antagonism (darting) and increased DA neurotransmission (locomotion, rearing, and grooming). Microinjection of CPP resulted in a significant increase in locomotion and darting in comparison to control animals. The levels of NMDA and DA-D₂ receptor mRNA was assessed in the cortex, striatum, and cerebellum of these animals by reverse transcription-polymerase chain reaction. No significant difference in NMDA mRNA was observed in any of the brain regions of CPP treated animals. However, a significant increase in striatal DA-D2 receptor mRNA was observed in animals received CPP. The results suggest a possible interaction between NMDA receptor activity in the prefrontal cortex and DA-D2 receptors in the striatum.