Search results for "Harm"
showing 10 items of 13866 documents
Subchronic vortioxetine treatment -but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex.
2017
Abstract Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT 3 -R, 5-HT 7 -R and 5-HT 1D -R antagonist, 5-HT 1B -R partial agonist, 5-HT 1A -R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p -chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of …
Taurine potentiates the anticonvulsive effect of the GABAAagonist muscimol and pentobarbital in the immature mouse hippocampus
2019
Objective The high incidence of epileptic seizures in neonates and their frequent refractoriness to pharmacologic therapies require identification of new therapeutical options. Therefore, we investigated whether the modulatory effect of taurine on γ-aminobutyric acid (GABA)A receptors can enhance the anticonvulsive potential of the GABAA receptor agonist muscimol and of the barbiturate pentobarbital. Methods We performed field potential recordings in in toto hippocampus preparations of immature (postnatal days 4-7) C57Bl/6 mouse pups. Spontaneous epileptiform activity was induced by the continuous presence of the potassium channel blocker 4-aminopyridine and the glycinergic antagonist stryc…
GABAA receptors in the ventral tegmental area control the outcome of a social competition in rats
2018
Social dominance can be attained through social competitions. Recent work in both humans and rodents has identified trait anxiety as a crucial predictor of social competitiveness. In addition, the anxiolytic GABAA positive modulator, diazepam, injected either systemically or into the ventral tegmental area (VTA) was shown to increase social dominance. Here, we investigated the impact of pharmacologically targeting GABAA receptors in the VTA for the outcome of a social competition between two unfamiliar male rats, one of them infused with vehicle and the other one with the drug under study. We show that infusion of the GABAA receptor agonist, muscimol, reduced anxiety-like behaviors and enha…
Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor.
2021
Cardiovascular outcome trials revealed cardiovascular benefits for type 2 diabetes mellitus patients when treated with long-acting glucagon-like peptide-1 (GLP-1) receptor agonists. In the last decade, major advances were made characterising the physiological effects of GLP-1 and its action on numerous targets including brain, liver, kidney, heart and blood vessels. However, the effects of GLP-1 and receptor agonists, and the GLP-1 receptor on the cardiovascular system have not been fully elucidated. We compare results from cardiovascular outcome trials of GLP-1 receptor agonists and review pleiotropic clinical and preclinical data concerning cardiovascular protection beyond glycaemic contr…
β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project
2016
β3-Adrenoceptor agonists were originally considered as a promising drug class for the treatment of obesity and/or type 2 diabetes. When these development efforts failed, they were repositioned for the treatment of the overactive bladder syndrome. Based on the example of the β3-adrenoceptor agonist mirabegron, but also taking into consideration evidence obtained with ritobegron and solabegron, we discuss challenges facing a translational pharmacology program accompanying clinical drug development for a first-in-class molecule. Challenges included generic ones such as ligand selectivity, species differences and drug target gene polymorphisms. Challenges that are more specific included changin…
5-HT1A Receptor Function Makes Wound Healing a Happier Process
2018
Skin wound healing is a multistage phenomenon that is regulated by cell–cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis reve…
β(3)‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?
2019
β(3)‐Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β(3)‐adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β(3)‐adrenoceptor agonist, are considerably lower than the EC(50) for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β(3)‐adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression o…
Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis.
2016
Background and Aims: Changes in gut serotonin content have been described in Inflammatory Bowel Disease and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous serotonin through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of Inflammatory Bowel Disease. Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135), 5-HT2A (Ketanserin), 5-HT…
The endocannabinoid-alcohol crosstalk: Recent advances on a bi-faceted target
2018
Increasing evidence has focusesed on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. In addition, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles i…
ALCOHOLIC LIVER DISEASE: A MOUSE MODEL REVEALS PROTECTION BY LACTOBACILLUS FERMENTUM
2016
Objectives Alcoholism is one of the most devastating diseases with high incidence, but knowledge of its pathology and treatment is still plagued with gaps mostly because of the inherent limitations of research with patients. We developed an animal model for studying liver histopathology, Hsp (heat-shock protein)-chaperones involvement, and response to treatment. Methods The system was standardized using mice to which ethanol was orally administered alone or in combination with Lactobacillus fermentum following a precise schedule over time and applying, at predetermined intervals, a battery of techniques (histology, immunohistochemistry, western blotting, real-time PCR, immunoprecipitation, …