title: Metabolic interactions between glutamatergic and dopaminergic neurotransmitter systems are mediated through D(1) dopamine receptors.
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.
authors: Instituto de Investigaciones Biomédicas Alberto Sols, CSIC/UAM, Madrid, Spain.
authors: Tiago B
authors: TB
authors: Rodrigues
authors: Noelia
authors: N
authors: Granado
authors: Oskar
authors: O
authors: Ortiz
authors: Sebastián
authors: S
authors: Cerdán
authors: Rosario
authors: R
authors: Moratalla
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D018698:Glutamic Acid; D004298:Dopamine