Possible involvement of the dopamine D2 receptors of ventromedial hypothalamus in the control of free- and scheduled-feeding and plasma ghrelin level in rat

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nasrin Mehranfard ◽  
Alireza Halabian ◽  
Hojatallah Alaei ◽  
Maryam Radahmadi ◽  
Zahra Bahari ◽  
...  
Keyword(s):  
Food Intake ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Ventromedial Hypothalamus ◽  
D2 Receptors ◽  
Ghrelin Level ◽  
Standard Diet ◽  
High Fat ◽  
Ghrelin Concentration ◽  
Dopamine D2

Abstract Objectives We investigated effect of the ventromedial hypothalamus (VMH) dopamine D2 receptor inhibition on food intake and plasma ghrelin following chronic free or scheduled meal with different caloric intakes. Methods Male Wistar rats (220–250 g) were fed diets containing free (control) or three scheduled diets of standard, restricted and high-fat for 1 month. The animals stereotaxically received an intra VMH single dose of sulpiride (0.005 µg)/or saline (0.5 µL) before meal time. Thirty minutes later, food intake and circulating ghrelin were measured. Results Sulpiride significantly reduced food intake and ghrelin concentration in freely fed and scheduled-standard diet (p<0.05), while increased food intake, with ghrelin level on fasted level in scheduled-restricted group (p<0.01) compared to control. Food intake and ghrelin concentration between scheduled-high fat and freely fed or scheduled-standard diets did not show significant changes. Conclusions The VMH D2 receptors are possibly involved in controlling scheduled eating behavior, depending on energy balance context.

The Effect of PAOPA, a Novel Allosteric Modulator of Dopamine D2 Receptors, on Select Signaling Proteins Following Sub-Chronic Administration in the Rat

2020 ◽  
Vol 13 ◽  
Author(s):  
Ritesh Daya ◽  
Joella Ho ◽  
Sharon Thomson ◽  
Jayant Bhandari ◽  
Ram K. Mishra
Keyword(s):  
Frontal Cortex ◽  
Mechanism Of Action ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
D2 Receptors ◽  
Dopamine D2 ◽  
Therapeutic Mechanism ◽  
Clinical Models ◽  
G Protein Coupled

Background: Allosteric modulators of G-protein coupled receptors regulate receptor activity by binding to sites other than the active site and have emerged as a new and highly desirable class of drugs. PAOPA (3(R)-[(2(S)- pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide), a peptidomimetic analog of Prolyl-Leucyl-Glycinamide, is a potent dopamine D2 receptor allosteric modulator. PAOPA has shown therapeutic effects in pre-clinical models of schizophrenia and extrapyramidal dysfunction. Objective: in this study, we sought to examine the biomolecular underpinnings of PAOPA‘s therapeutic outcomes in preclinical models of schizophrenia. Method: Following sub-chronic (daily for 7 days) administration of PAOPA, we assessed levels of dopamine D2 receptors, receptor kinases (GRK2 (G protein-coupled receptor kinase 2) and Arrestin-3), and phosphorylated mitogenactivated protein kinase (MAPKs), namely, extracellular signal-regulated kinases (ERK1/2) in the hippocampus, medial pre-frontal cortex, nucleus accumbens, pre-frontal cortex, and dorsal striatum via protein quantification. Results: Following 7 days of daily PAOPA treatment, we observed decreased GRK2 and increased dopamine D2 receptor expression in the dorsal striatum. These findings potentially underscore PAOPA’s therapeutic mechanism of action for the positive-like symptoms of schizophrenia in pre-clinical animal models. Additionally, we observed a decline in GRK2 in the hippocampus and an increase in phosphorylated ERK1 in the pre-frontal cortex, suggestive of a role for PAOPA in treating cognitive and/or affective dysfunction in pre-clinical models. Conclusion: While further studies are required to elucidate PAOPA’s mechanism of action, this study builds on prior investigations and develops an early framework to describe the therapeutic mechanism of action of PAOPA.

scholarly journals Effect of Zishenpingchan Granule on Neurobehavioral Manifestations and the Activity and Gene Expression of Striatal Dopamine D1 and D2 Receptors of Rats with Levodopa-Induced Dyskinesias

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Ye ◽  
Xiao-Lei Yuan ◽  
Jie Zhou ◽  
Can-xing Yuan ◽  
Xu-ming Yang
Keyword(s):  
Gene Expression ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
D2 Receptors ◽  
Striatal Dopamine ◽  
Control Group ◽  
Indirect Pathway ◽  
Dopamine D2 ◽  
D1 And D2 Receptors ◽  
Neurobehavioral Manifestations

This study was performed to observe the effects of Zishenpingchan granule on neurobehavioral manifestations and the activity and gene expression of striatal dopamine D1 and D2 receptors of rats with levodopa-induced dyskinesias (LID). We established normal control group, LID model group, and TCM intervention group. Each group received treatment for 4 weeks. Artificial neural network (ANN) was applied to excavate the main factor influencing variation in neurobehavioral manifestations of rats with LID. The results showed that overactivation in direct pathway mediated by dopamine D1 receptor and overinhibition in indirect pathway mediated by dopamine D2 receptor may be the main mechanism of LID. TCM increased the efficacy time of LD to ameliorate LID symptoms effectively mainly by upregulating dopamine D2 receptor gene expression.

Dopamine D2 Receptor Blockade and Antimigraine Action of Flunarizine

Cephalalgia ◽  
1994 ◽  
Vol 14 (3) ◽  
pp. 235-240 ◽  
Author(s):  
C Wöber ◽  
T Brücke ◽  
C Wöber-Bingöl ◽  
S Asenbaum ◽  
P Wessely ◽  
...  
Keyword(s):  
Single Photon ◽  
Dopamine D2 Receptor ◽  
Photon Emission ◽  
D2 Receptor ◽  
High Specificity ◽  
D2 Receptors ◽  
Binding Potential ◽  
Receptor Blockade ◽  
Dopamine D2

We studied in vivo the influence of flunarizine on dopamine D2 receptors and investigated whether dopamine D2 receptor blockade is involved in its antimigraine action. Eleven migraine patients, treated with flunarizine, 10 mg per day, underwent single photon emission computer tomography (SPECT) using [123I] labeled iodobenzamide, a ligand with high affinity and high specificity for D2 receptors. There was a reduction of the dopamine D2 receptor binding potential in all patients compared to age-matched controls. The efficacy of flunarizine in migraine prophylaxis failed to correlate with the degree of the dopamine D2 receptor blockade. The antimigraine action of flunarizine may not involve antidopaminergic mechanisms.

scholarly journals Leptin reduces food intake via a dopamine D2 receptor-dependent mechanism

2012 ◽  
Vol 1 (1-2) ◽  
pp. 86-93 ◽  
Author(s):  
Sonja K. Billes ◽  
Stephanie E. Simonds ◽  
Michael A. Cowley
Keyword(s):  
Food Intake ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2 ◽  
Dependent Mechanism

scholarly journals Diagnostic imaging of dopamine receptors in pituitary adenomas

2007 ◽  
Vol 156 (suppl_1) ◽  
pp. S53-S56 ◽  
Author(s):  
Wouter W de Herder ◽  
Ambroos E M Reijs ◽  
Richard A Feelders ◽  
Maarten O van Aken ◽  
Eric P Krenning ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Single Photon ◽  
Dopamine D2 Receptor ◽  
Photon Emission ◽  
D2 Receptor ◽  
Pituitary Tumour ◽  
D2 Receptors ◽  
Emission Computed Tomography ◽  
Dopamine D2 ◽  
Pituitary Macroadenomas

Dopamine D2 receptor scintigraphy of pituitary adenomas is feasible by single-photon emission computed tomography using 123I-S-(−)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6-methoxybenzamide (123I-IBZM) and 123I-epidepride. 123I-epidepride is generally superior to 123I-IBZM for the visualization of D2 receptors on pituitary macroadenomas. However, 123I-IBZM and 123I-epidepride scintigraphy are generally not useful to predict the response to dopaminergic treatment in pituitary tumour patients. These techniques might allow discrimination of non-functioning pituitary macroadenomas from other non-tumour pathologies in the sellar region. Dopamine D2 receptors on pituitary tumours can also be studied using positron emission tomography with 11C-N-raclopride and 11C-N-methylspiperone.

scholarly journals Distinct Dopamine D2 Receptor Antagonists Differentially Impact D2 Receptor Oligomerization

2019 ◽  
Vol 20 (7) ◽  
pp. 1686 ◽  
Author(s):  
Elise Wouters ◽  
Adrián Marín ◽  
James Dalton ◽  
Jesús Giraldo ◽  
Christophe Stove
Keyword(s):  
Dopamine D2 Receptor ◽  
Critical Role ◽  
D2 Receptor ◽  
D2 Receptors ◽  
Reporter Assay ◽  
Dimer Formation ◽  
Dopamine D2 ◽  
Receptor Oligomerization ◽  
Pathological Conditions

Dopamine D2 receptors (D2R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development of schizophrenia. Pharmacological targeting and modulation of the equilibrium of these receptor homodimers might lead to a better understanding of the critical role played by these complexes in physiological and pathological conditions. Whereas agonist addition has shown to prolong the D2R dimer lifetime and increase the level of dimer formation, the possible influence of D2R antagonists on dimerization has remained rather unexplored. Here, using a live-cell reporter assay based on the functional complementation of a split Nanoluciferase, a panel of six D2R antagonists were screened for their ability to modulate the level of D2LR dimer formation. Incubation with the D2R antagonist spiperone decreased the level of D2LR dimer formation significantly by 40–60% in real-time and after long-term (≥16 h) incubations. The fact that dimer formation of the well-studied A2a–D2LR dimer was not altered following incubation with spiperone supports the specificity of this observation. Other D2R antagonists, such as clozapine, risperidone, and droperidol did not significantly evoke this dissociation event. Furthermore, molecular modeling reveals that spiperone presents specific Tyr1995.48 and Phe3906.52 conformations, compared to clozapine, which may determine D2R homodimerization.

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