Mice lacking the dopamine D4 receptor subtype (D4R-/-) are supersensitive to methamphetamine and cocaine. We sought to expand and refine earlier experiments performed on F2 generation D4R-/- mice by lengthening the behavioral session, utilizing an N10 D4R-/- incipient congenic C57BL/6J line (D4R-/- mice backcrossed with wildtype C57BL/6J mice for 10 successive generations), and investigating whether dopamine D4Rs are necessary for the expression of behavioral sensitization to amphetamine. The D4R-/- mice demonstrated an enhanced and dose-dependent increase in amphetamine-stimulated activity compared to wildtype mice following acute administrations of amphetamine. For the behavioral sensitization experiments, separate groups of mice received either repeated administrations of the same dose of amphetamine or a subthreshold dose of amphetamine (2 mg/kg) 28 days following pretreatment with either saline, 1.0, 3.0, or 10.0 mg/kg amphetamine. The D4R-/- mice displayed an enhanced dose-dependent sensitized response to repeated amphetamine administrations compared to their wildtype littermates in both behavioral sensitization paradigms. Our present results further support the importance of dopamine D4Rs in psychostimulant-mediated locomotion and neural plasticity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/syn.20043 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sleep-sensitive dopamine receptor expression in male mice underlies attention deficits after a critical period of early adversity.
Sci Transl Med
October 2024
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Article Synopsis
- Early life stress (ELS) in mice leads to cognitive issues and changes in dopamine receptor expression in the male offspring's anterior cingulate cortex (ACC).
- Fragmented maternal care during a critical neonatal period resulted in elevated D2R and suppressed D4R, impairing performance on visual attention tasks, but this could be reversed in adulthood through pharmacological interventions.
- ELS male mice also exhibited increased hypothalamic orexin and disrupted sleep patterns, pointing to sleep loss as a possible underlying factor for cognitive deficits, a correlation that extends to attention issues observed in children who experienced early adversity.
Impaired dopamine signaling in early diabetic retina: Insights from D1R and D4R agonist effects on whole retina responses.
Exp Eye Res
October 2024
Department of Physiology, University of Arizona, Tucson, AZ, USA; Department of Biomedical Engineering, University of Arizona, Tucson, AZ, USA. Electronic address:
The retina has low dopamine levels early in diabetes. To determine how low dopamine levels affected dopamine signaling, the effects of dopamine receptor agonists and mRNA localization were measured after 6 weeks of diabetes. Whole retina ex vivo electroretinogram (ERG) recordings were used to analyze how dopamine type 1 receptor (D1R) and type 4 (D4R) agonists change the light-evoked retinal responses of non-diabetic and 6-week diabetic (STZ injected) mouse retinas.
View Article and Find Full Text PDFThe salt sensitivity of Drd4-null mice is associated with the upregulations of sodium transporters in kidneys.
Hypertens Res
August 2024
The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China.
To explore the mechanism of the hypertension in dopamine receptor-4 (Drd4) null mice, we determined the salt sensitivity and renal sodium transport proteins in Drd4 and Drd4 mice with varied salt diets. On normal NaCl diet (NS), mean arterial pressures (MAP, telemetry) were higher in Drd4 than Drd4; Low NaCl diet (LS) tended to decrease MAP in both strains; high NaCl diet (HS) elevated MAP with sodium excretion decreased and pressure-natriuresis curve shifted to right in Drd4 relative to Drd4 mice. Drd4 mice exhibited increased renal sodium-hydrogen exchanger 3 (NHE3), sodium-potassium-2-chloride cotransporter (NKCC2), sodium-chloride cotransporter (NCC), and outer medullary α-epithelial sodium channel (αENaC) on NS, decreased NKCC2, NCC, αENaC, and αNa-K-ATPase on LS, and increased αENaC on HS.
View Article and Find Full Text PDFBackground: The thiazide-sensitive sodium chloride cotransporter (NCC) is the major apical sodium transporter located in the mammalian renal distal convoluted tubule (DCT). The amount of sodium reabsorbed in the DCT through NCC plays an important role in the regulation of extracellular fluid volume and blood pressure. Dopamine and its receptors constitute a renal antihypertensive system in mammals.
View Article and Find Full Text PDFDopamine Receptor DR and DR and GRK4 Interaction in Hypertension.
Yale J Biol Med
March 2023
Division of Kidney Diseases and Hypertension, Department of Medicine, The George Washington School of Medicine and Health Sciences, Washington, DC, USA.
Essential hypertension is caused by the interaction of genetic, behavioral, and environmental factors. Abnormalities in the regulation of renal ion transport cause essential hypertension. The renal dopaminergic system, which inhibits sodium transport in all the nephron segments, is responsible for at least 50% of renal sodium excretion under conditions of moderate sodium excess.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!