Intracerebroventricular injection of ouabain causes mania-like behavior in mice through D2 receptor activation

Abstract Intracerebroventricular (ICV) administration of ouabain, an inhibitor of the Na, K-ATPase, is an approach used to study the physiological functions of the Na, K-ATPase and cardiotonic steroids in the central nervous system, known to cause mania-like hyperactivity in rats. We describe a mouse model of ouabain-induced mania-like behavior. ICV administration of 0.5 µl of 50 µM (25 pmol, 14.6 ng) ouabain into each lateral brain ventricle results in increased locomotor activity, stereotypical behavior, and decreased anxiety level an hour at minimum. Fast-scan cyclic voltammetry showed that administration of 50 µM ouabain causes a drastic drop in dopamine uptake rate, confirmed by elevated concentrations of dopamine metabolites detected in the striatum 1 h after administration. Ouabain administration also caused activation of Akt, deactivation of GSK3β and activation of ERK1/2 in the striatum of ouabain-treated mice. All of the abovementioned effects are attenuated by haloperidol (70 µg/kg intraperitoneally). Observed effects were not associated with neurotoxicity, since no dystrophic neuron changes in brain structures were demonstrated by histological analysis. This newly developed mouse model of ouabain-induced mania-like behavior could provide a perspective tool for studying the interactions between the Na,K-ATPase and the dopaminergic system.

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Role of the Dopaminergic System in the Striatum and Its Association With Functional Recovery or Rehabilitation After Brain Injury

Frontiers in Neuroscience ◽

10.3389/fnins.2021.693404 ◽

2021 ◽

Vol 15 ◽

Author(s):

Antonio Verduzco-Mendoza ◽

Paul Carrillo-Mora ◽

Alberto Avila-Luna ◽

Arturo Gálvez-Rosas ◽

Adriana Olmos-Hernández ◽

...

Keyword(s):

Brain Injury ◽

Functional Recovery ◽

Dopaminergic System ◽

Brain Structures ◽

Receptor Activation ◽

Important Goal ◽

Dopaminergic Drugs ◽

Beneficial Effects ◽

Severe Tbi

Disabilities are estimated to occur in approximately 2% of survivors of traumatic brain injury (TBI) worldwide, and disability may persist even decades after brain injury. Facilitation or modulation of functional recovery is an important goal of rehabilitation in all patients who survive severe TBI. However, this recovery tends to vary among patients because it is affected by the biological and physical characteristics of the patients; the types, doses, and application regimens of the drugs used; and clinical indications. In clinical practice, diverse dopaminergic drugs with various dosing and application procedures are used for TBI. Previous studies have shown that dopamine (DA) neurotransmission is disrupted following moderate to severe TBI and have reported beneficial effects of drugs that affect the dopaminergic system. However, the mechanisms of action of dopaminergic drugs have not been completely clarified, partly because dopaminergic receptor activation can lead to restoration of the pathway of the corticobasal ganglia after injury in brain structures with high densities of these receptors. This review aims to provide an overview of the functionality of the dopaminergic system in the striatum and its roles in functional recovery or rehabilitation after TBI.

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Altered responses to dopaminergic D2 receptor activation and N-type calcium currents in striatal cholinergic interneurons in a mouse model of DYT1 dystonia

Neurobiology of Disease ◽

10.1016/j.nbd.2006.07.006 ◽

2006 ◽

Vol 24 (2) ◽

pp. 318-325 ◽

Cited By ~ 105

Author(s):

A. Pisani ◽

G. Martella ◽

A. Tscherter ◽

P. Bonsi ◽

N. Sharma ◽

...

Keyword(s):

Mouse Model ◽

D2 Receptor ◽

Receptor Activation ◽

Calcium Currents ◽

Cholinergic Interneurons ◽

Dyt1 Dystonia

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Delta sleep-inducing peptide (DSIP) effect on brain structures of August and Wistar rats under dopaminergic system hyperfunction

PsycEXTRA Dataset ◽

10.1037/e516032012-079 ◽

2004 ◽

Author(s):

A. V. Sergutina ◽

L. M. Gershtein

Keyword(s):

Wistar Rats ◽

Dopaminergic System ◽

Brain Structures ◽

August And Wistar Rats ◽

Delta Sleep ◽

Delta Sleep Inducing Peptide

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Central Histamine, the H3-Receptor and Obesity Therapy

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190703094846 ◽

2019 ◽

Vol 18 (7) ◽

pp. 516-522

Author(s):

Néstor F. Díaz ◽

Héctor Flores-Herrera ◽

Guadalupe García-López ◽

Anayansi Molina-Hernández

Keyword(s):

Body Weight ◽

Food Intake ◽

Animal Studies ◽

Energy Homeostasis ◽

Receptor Activation ◽

Receptor Ligands ◽

Histaminergic System ◽

H3 Receptor ◽

Weight One ◽

The Central Nervous System

The brain histaminergic system plays a pivotal role in energy homeostasis, through H1- receptor activation, it increases the hypothalamic release of histamine that decreases food intake and reduces body weight. One way to increase the release of hypothalamic histamine is through the use of antagonist/inverse agonist for the H3-receptor. Histamine H3-receptors are auto-receptors and heteroreceptors located on the presynaptic membranes and cell soma of neurons, where they negatively regulate the synthesis and release of histamine and other neurotransmitters in the central nervous system. Although several compounds acting as H3-receptor antagonist/inverse agonists have been developed, conflicting results have been reported and only one has been tested as anti-obesity in humans. Animal studies revealed the opposite effect in food intake, energy expeditor, and body weight, depending on the drug, spice, and route of administration, among others. The present review will explore the state of art on the effects of H3-receptor ligands on appetite and body-weight, going through the following: a brief overview of the circuit involved in the control of food intake and energy homeostasis, the participation of the histaminergic system in food intake and body weight, and the H3-receptor as a potential therapeutic target for obesity.

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The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models

Molecules ◽

10.3390/molecules26051372 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1372

Author(s):

Tengrui Shi ◽

Jianxi Song ◽

Guanying You ◽

Yujie Yang ◽

Qiong Liu ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Synaptic Plasticity ◽

Mouse Model ◽

Mouse Models ◽

Knockout Mouse ◽

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductase ◽

Knockout Mouse Model ◽

The Central Nervous System

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.

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Male Fetal Sex Affects Uteroplacental Angiogenesis in Growth Restriction Mouse Model†

Biology of Reproduction ◽

10.1093/biolre/ioab006 ◽

2021 ◽

Author(s):

Jessica F Hebert ◽

Jess A Millar ◽

Rahul Raghavan ◽

Amie Romney ◽

Jason E Podrabsky ◽

...

Keyword(s):

Mouse Model ◽

Killer Cell ◽

Receptor Activation ◽

Growth Restriction ◽

Late Gestation ◽

Spiral Artery ◽

Micro Computed Tomography ◽

Fetal Sex ◽

Maternal Genotype ◽

Agt Gene

Abstract Abnormally increased angiotensin II activity related to maternal angiotensinogen (AGT) genetic variants, or aberrant receptor activation, is associated with small-for-gestational-age (SGA) babies and abnormal uterine spiral artery remodeling in humans. Our group studies a murine AGT gene titration transgenic (TG; 3-copies of the AGT gene) model, which has a 20% increase in AGT expression mimicking a common human AGT genetic variant (A[−6]G) associated with intrauterine growth restriction (IUGR) and spiral artery pathology. We hypothesized that aberrant maternal AGT expression impacts pregnancy-induced uterine spiral artery angiogenesis in this mouse model leading to IUGR. We controlled for fetal sex and fetal genotype (e.g., only 2-copy wild-type [WT] progeny from WT and TG dams were included). Uteroplacental samples from WT and TG dams from early (days 6.5 and 8.5), mid (d12.5), and late (d16.5) gestation were studied to assess uterine natural killer cell (uNK) phenotypes, decidual metrial triangle angiogenic factors, placental growth and capillary density, placental transcriptomics, and placental nutrient transport. Spiral artery architecture was evaluated at day 16.5 by contrast-perfused three-dimensional micro-computed tomography (3D microCT). Our results suggest that uteroplacental angiogenesis is significantly reduced in TG dams at day 16.5. Males from TG dams are associated with significantly reduced uteroplacental angiogenesis from early to late gestation compared with their female littermates and WT controls. Angiogenesis was not different between fetal sexes from WT dams. We conclude that male fetal sex compounds the pathologic impact of maternal genotype in this mouse model of growth restriction.

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The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats

Neurochemical Research ◽

10.1007/s11064-021-03238-9 ◽

2021 ◽

Author(s):

Zhanglei Dong ◽

Bingwu Huang ◽

Chenchen Jiang ◽

Jiangfan Chen ◽

Han Lin ◽

...

Keyword(s):

Nucleus Accumbens ◽

D2 Receptor ◽

Fixed Ratio ◽

Receptor Activation ◽

Addictive Behaviors ◽

Self Administration ◽

A2a Receptors ◽

Mediated Effects ◽

Seeking Behavior ◽

Adenosine A2a

AbstractPropofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5–10.0 ng/site), MSX-3 (A2AR antagonist, 5.0–20.0 μg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75–3.0 μg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75–3.0 μg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0–20.0 μg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

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