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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/jnr.21302 | DOI Listing |
Mol Psychiatry
January 2025
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli, 80078, Naples, Italy.
Lysosomal storage disorders characterized by defective heparan sulfate (HS) degradation, such as Mucopolysaccharidosis type IIIA-D (MPS-IIIA-D), result in neurodegeneration and dementia in children. However, dementia is preceded by severe autistic-like behaviours (ALBs), presenting as hyperactivity, stereotypies, social interaction deficits, and sleep disturbances. The absence of experimental studies on ALBs' mechanisms in MPS-III has led clinicians to adopt symptomatic treatments, such as antipsychotics, which are used for non-genetic neuropsychiatric disorders.
View Article and Find Full Text PDFBiol Psychiatry
January 2025
Institute of Biology Paris-Seine, laboratory Neuroscience Paris-Seine, CNRS, INSERM, Sorbonne Université, UPMC Université Paris 06 F-75005, Paris, France. Electronic address:
Background: The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens (NAc)).
View Article and Find Full Text PDFExp Eye Res
January 2025
Department of Ophthalmology, The Second Hospital &Clinical Medical School, Lanzhou University, Gansu, 730000, China. Electronic address:
The mechanisms underlying the low incidence of myopia at high altitudes remain unclear. Choroidal thickness and the dopaminergic system have been shown to be closely associated with myopia development. This study aimed to investigate the effects of high altitude exposure on choroidal thickness and the dopaminergic system.
View Article and Find Full Text PDFAt cellular and circuit levels, drug addiction is considered a dysregulation of synaptic plasticity. In addition, dysfunction of the glutamate transporter 1 (GLT-1) in the nucleus accumbens (NAc) has also been proposed as a mechanism underlying drug addiction. However, the cellular and synaptic impact of GLT-1 alterations in the NAc remain unclear.
View Article and Find Full Text PDFPhytomedicine
January 2025
Department of Anesthesiology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu Province, PR China; Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, PR China. Electronic address:
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!