A5010158051- Cannabis and Cannabinoid Research
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Diet, Metabolism, and Disease
- Sleep and Wakefulness Research
- Pancreatic function and diabetes
- Diet and metabolism studies
- Pharmacological Receptor Mechanisms and Effects
- Alcohol Consumption and Health Effects
- Forensic Toxicology and Drug Analysis
- Biochemical effects in animals
- Dietary Effects on Health
- Biochemical Analysis and Sensing Techniques
- Neuroscience of respiration and sleep
- Pain Mechanisms and Treatments
- Adipose Tissue and Metabolism
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Prenatal Substance Exposure Effects
- GABA and Rice Research
- Immune cells in cancer
- Estrogen and related hormone effects
- Diabetes Management and Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neutropenia and Cancer Infections
Northeastern University
2015-2024
North Carolina School of Science and Mathematics
2024
Uppsala University
2023
Universidad del Noreste
2020
University of Southern California
2019
McLean Hospital
2012-2019
Scripps Research Institute
2019
ShanghaiTech University
2019
Harvard University
2012-2019
Indiana University Bloomington
2018
Obesity and its metabolic consequences are a major public health concern worldwide. is associated with overactivity of the endocannabinoid system, which involved in regulation appetite, lipogenesis, insulin resistance. Cannabinoid-1 receptor (CB1R) antagonists reduce body weight improve cardiometabolic abnormalities experimental human obesity, but their therapeutic potential limited by neuropsychiatric side effects. Here we have demonstrated that CB1R neutral antagonist largely restricted to...
The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of without psychoactivity CB1 has therapeutic potential inflammatory, fibrotic, neurodegenerative diseases. Here, we report crystal structure human complex with a rationally designed antagonist, AM10257, at 2.8 Å resolution. CB2-AM10257 reveals distinctly different binding pose compared CB1. However, extracellular portion antagonist-bound shares high degree conformational similarity...
Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks high response requirements, instead select less effortful food-seeking behaviors. In the present study, effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on PROG schedule reinforced by...
Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity, and associated diseases, imposing a costly burden on current health care. Cannabinoid receptor type-1 (CB1) plays crucial role in controlling metabolism through central peripheral mechanisms. In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1–KO) was sufficient protect adult mice from diet-induced obesity metabolic alterations reverse phenotype already obese mice. Compared with controls,...
Glucocorticoids are known to promote the development of metabolic syndrome through modulation both feeding pathways and processes; however, precise mechanisms these effects not well-understood. Recent evidence shows that glucocorticoids possess ability increase endocannabinoid signaling, which is regulate appetite, energy balance, processes central peripheral pathways. The aim this study was determine role signaling in glucocorticoid-mediated obesity syndrome. Using a mouse model excess...
Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations reinforcement value response costs. Furthermore, people with major depression other disorders often show anergia, psychomotor retardation, fatigue, alterations in decision making. Tasks measuring effort-based making can be used as animal models the motivational symptoms depression, present studies characterized effects vesicular monoamine transport...
Background: Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed AM1710, a cannabilactone 2 agonist, produces antinociception without producing central nervous system (CNS)-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models neuropathic pain evoked by diverse chemotherapeutic (cisplatin and paclitaxel). A secondary objective investigate...
ABSTRACT The cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse nicotine‐seeking behaviour abstinent subjects based on actions (CB) receptor antagonists. However, CB stimulation self‐administration reinstatement have not been systematically studied. Here, we studied WIN 55,212‐2, CB1/2 agonist, intravenous under fixed‐ratio (FR) progressive‐ratio (PR) schedules reinforcement rats. 55,212‐2 responding for food similar...
Background and Purpose CB 1 receptor signalling is canonically mediated through inhibitory Gα i proteins, but occurs other G proteins under some circumstances, s being the most characterized secondary pathway. Determinants of this switch identified to date include blockade, /D 2 co‐stimulation, agonist class cell background. Hence, we examined effects number different ligands on signalling. Experimental Approach receptors were expressed in HEK cells at levels, for cAMP by real‐time BRET...
Multiple studies suggest a pivotal role of the endocannabinoid system in regulating reinforcing effects various substances abuse. Rimonabant, CB1 inverse agonist found to be effective for smoking cessation, was associated with an increased risk anxiety and depression. Here we evaluated neutral antagonist AM4113 on abuse-related nicotine its depressive-like behavior rats. Rats were trained self-administer under fixed-ratio 5 or progressive-ratio schedules reinforcement. A control group food....
Cannabinoid (CB)1 receptor inverse agonists inhibit food intake in animals and humans but also potentiate emesis. It is not clear whether these effects result from agonist properties or the blockade of endogenous cannabinoid signaling. Here, we examine effect a neutral CB1 antagonist, AM4113, on intake, weight gain, Neutral antagonist binding were confirmed HEK-293 cells transfected with human CB2 receptors. AM4113 had no forskolin-stimulated cAMP production at concentrations up to 630 nM....
Chemotherapeutic treatment results in chronic pain an estimated 30-40 percent of patients. Limited and often ineffective treatments make the need for new therapeutics urgent one. We compared effects prophylactic cannabinoids as a preventative strategy suppressing development paclitaxel-induced nociception. The mixed CB1/CB2 agonist WIN55,212-2 was with cannabilactone CB2-selective AM1710, administered subcutaneously (s.c.), via osmotic mini pumps before, during, after paclitaxel treatment....
The morbidity and mortality associated with recreational use of synthetic cannabinoid receptor agonists (SCRAs) may reflect strong activation CB1 receptors is a major health concern. properties SCRA at are not well defined. Here we have developed an assay to determine acute efficacy using depletion the irreversible antagonist AM6544, application Black Leff operational model calculate efficacy.Receptor in mouse AtT-20 pituitary adenoma cells stably expressing human was achieved by...
Background Cannabinoid type 1 (CB1) receptors are involved in the regulation of gastrointestinal (GI) motility and secretion. Our aim was to characterize roles CB1 receptor on GI secretion vitro vivo by using different classes antagonists. Methods Immunohistochemistry used examine localization mouse ileum colon. Organ bath experiments testing comprising upper transit, colonic expulsion, whole gut transit were performed effects inverse agonist/antagonist AM251 neutral antagonist AM4113. As a...
The endocannabinoid system has been implicated in the pathogenesis of diabetic nephropathy (DN). We investigated effect combined therapy with AM6545, a 'peripherally' restricted cannabinoid receptor type 1 (CB1R) neutral antagonist, and AM1241, 2 (CB2R) agonist, experimental DN.Renal function structure, podocyte proteins markers both fibrosis inflammation were studied streptozotocin-induced mice treated for 14 weeks vehicle, AM1241 AM6545-AM1241.Single treatment either AM6545 or alone...