• dopamine;
  • glutamate;
  • dopamine D1 and D2 receptors;
  • 13C-NMR;
  • Parkinson's disease, striatum


Interactions between the dopaminergic and glutamatergic neurotransmission systems were investigated in the adult brain of wild-type (WT) and transgenic mice lacking the dopamine D1 or D2 receptor subtypes. Activity of the glutamine cycle was evaluated by using 13C NMR spectroscopy, and striatal activity was assessed by c-Fos expression and motor coordination. Brain extracts from (1,2-13C2) acetate-infused mice were prepared and analyzed by 13C NMR to determine the incorporation of the label into the C4 and C5 carbons of glutamate and glutamine. D1R−/− mice showed a significantly higher concentration of cerebral (4,5-13C2) glutamine, consistent with an increased activity of the glutamate-glutamine cycle and of glutamatergic neurotransmission. Conversely, D2R−/− mice did not show any significant changes in (4,5-13C2) glutamate or (4,5-13C2) glutamine, suggesting that alterations in glutamine metabolism are mediated through D1 receptors. This was confirmed with D1R−/− and WT mice treated with reserpine, a dopamine-depleting drug, or with reserpine followed by L-DOPA, a dopamine precursor. Exposure to reserpine increased (4,5-13C2) glutamine in WT to levels similar to those found in untreated D1R−/− mice. These values were the same as those reached in the reserpine-treated D1R−/− mice. Treatment of WT animals with L-DOPA returned (4,5-13C2) glutamine levels to normal, but this was not verified in D1R−/− animals. Reserpine impaired motor coordination and decreased c-Fos expression, whereas L-DOPA restored both variables to normal values in WT but not in D1R−/−. Together, our results reveal novel neurometabolic interactions between glutamatergic and dopaminergic systems that are mediated through the D1, but not the D2, dopamine receptor subtype. © 2007 Wiley-Liss, Inc.