Effect of intracerebral administration of NMDA and AMPA on dopamine and glutamate release in the ventral pallidum and on motor behavior

The present study investigates the modulation of the ventral tegmental area (VTA)-ventral pallidum (VP) dopaminergic system by glutamate agonists in r ats. The glutamate receptor agonists N-methyl-D-aspartate (NMDA) and alpha- amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) were infused via reversed microdialysis into the VTA, and dopamine (DA), glutamate, and asp artate levels in the VTA and ipsilateral VP were monitored together with mo tor behavior screened in an open field. NMDA (750 mu M) infusion, as well a s AMPA (50 mu M) infusion, induced an increase of DA and glutamate levels i n the VTA, followed by an increase of DA levels in the ipsilateral VP and b y enhanced locomotor activity. The increase of DA in the VP was similar aft er administration of these two glutamate agonists, although motor activity was more pronounced and showed an earlier onset after NMDA infusion. Glutam ate levels in the VP were not increased by the stimulation of DA release. I t is concluded that DA is released from mesencephalic DA neurons projecting to the VP and that these neurons are controlled by glutamatergic systems, via NMDA and AMPA receptors. Thus, DA in the VP has to be considered as a s ubstantial modulator. Dysregulation of the mesopallidal DA neurons, as well as their glutamatergic control, may play an additional or distinct role in disorders like schizophrenia and drug addiction.