Metabolic interactions between glutamatergic and dopaminergic neurotransmitter systems are mediated through D1 dopamine receptors
✍ Scribed by Tiago B. Rodrigues; Noelia Granado; Oskar Ortiz; Sebastián Cerdán; Rosario Moratalla
- Book ID
- 102382561
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 356 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Interactions between the dopaminergic and glutamatergic neurotransmission systems were investigated in the adult brain of wild‐type (WT) and transgenic mice lacking the dopamine D~1~ or D~2~ receptor subtypes. Activity of the glutamine cycle was evaluated by using ^13^C NMR spectroscopy, and striatal activity was assessed by c‐Fos expression and motor coordination. Brain extracts from (1,2‐^13^C~2~) acetate‐infused mice were prepared and analyzed by ^13^C NMR to determine the incorporation of the label into the C4 and C5 carbons of glutamate and glutamine. D~1~R^−/−^ mice showed a significantly higher concentration of cerebral (4,5‐^13^C~2~) glutamine, consistent with an increased activity of the glutamate‐glutamine cycle and of glutamatergic neurotransmission. Conversely, D~2~R^−/−^ mice did not show any significant changes in (4,5‐^13^C~2~) glutamate or (4,5‐^13^C~2~) glutamine, suggesting that alterations in glutamine metabolism are mediated through D~1~ receptors. This was confirmed with D~1~R^−/−^ 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‐^13^C~2~) glutamine in WT to levels similar to those found in untreated D~1~R^−/−^ mice. These values were the same as those reached in the reserpine‐treated D~1~R^−/−^ mice. Treatment of WT animals with L‐DOPA returned (4,5‐^13^C~2~) glutamine levels to normal, but this was not verified in D~1~R^−/−^ animals. Reserpine impaired motor coordination and decreased c‐Fos expression, whereas L‐DOPA restored both variables to normal values in WT but not in D~1~R^−/−^. Together, our results reveal novel neurometabolic interactions between glutamatergic and dopaminergic systems that are mediated through the D~1~, but not the D~2~, dopamine receptor subtype. © 2007 Wiley‐Liss, Inc.