Cannabinoid 1 (CB1) receptor antagonists reduce body weight and improve insulin sensitivity. Preclinical data indicates that an acute dose of CB1 antagonist rimonabant causes an increase in blood glucose. A stable analog of glucagon-like peptide 1 (GLP-1), exendin-4 improves glucose-stimulated insulin secretion in pancreas, and reduces appetite through activation of GLP-1 receptors in the central nervous system and liver. We hypothesized that the insulin secretagogue effect of GLP-1 agonist exendin-4 may synergize with the insulin-sensitizing action of rimonabant. Intraperitoneal as well as intracerebroventricular administration of rimonabant increased serum glucose upon glucose challenge in overnight fasted, diet-induced obese C57 mice, with concomitant rise in serum glucagon levels. Exendin-4 reversed the acute hyperglycemia induced by rimonabant. The combination of exendin-4 and rimonabant showed an additive effect in the food intake, and sustained body weight reduction upon repeated dosing. The acute efficacy of both the compounds was additive for inducing nausea-like symptoms in conditioned aversion test in mice, whereas exendin-4 treatment antagonized the effect of rimonabant on forced swim test upon chronic dosing. Thus, the addition of exendin-4 to rimonabant produces greater reduction in food intake owing to increased aversion, but reduces the other central nervous system side effects of rimonabant. The hyperglucagonemia induced by rimonabant is partially responsible for enhancing the antiobesity effect of exendin-4.
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http://dx.doi.org/10.1139/cjpp-2014-0310 | DOI Listing |
Pharmacol Res
December 2024
Department of Biomedicine, Aarhus University, Denmark; Translational Neuropsychiatry Unit, Aarhus University, Denmark. Electronic address:
Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL). S-KET (15 mg/kg) effects were assessed in rats exposed to the open field and forced swimming test (FST), followed by analysis of the eCB signaling in the rat prefrontal cortex (PFC), a brain region involved in depression neurobiology.
View Article and Find Full Text PDFLife Sci
December 2024
Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium. Electronic address:
Skeletal muscle regeneration upon injury requires timely activation of inflammatory, myogenic, fibrotic, apoptotic and anabolic systems. Optimization of these features might improve the recovery process. Whereas recent data indicate that the endocannabinoid system, and more particularly cannabinoid receptor 1 (CB1) antagonism, is involved in the regulation of inflammatory, myogenic, fibrotic, apoptotic and anabolic pathways, it was never studied whether CB1 antagonism can improve muscle regeneration.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
December 2024
The Gill Institute for Neuroscience, Indiana University, Bloomington, Indiana, United States.
Purpose: We have shown that cannabinoid CB1 receptors regulate both salivation and tearing, but for tearing, this regulation is sex dependent with opposing effects by sex. We investigated a potential interplay of circadian and cannabinoid regulation of tearing.
Methods: We measured cannabinoid and circadian regulation of tearing in CD1 strain mice as well as CB1 receptor protein expression using immunohistochemistry.
Curr Diab Rep
November 2024
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, 5841 S. Maryland Ave, MC1027, Chicago, IL, 60637, USA.
Neurosci Lett
January 2025
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, NY, USA; Department of Psychology, State University at Buffalo, Buffalo, NY, USA. Electronic address:
Fatty acid-binding protein 7 (FABP7) aids in the intracellular transport of endogenous cannabinoids and is involved in regulating the stress response system. This study examined the role of FABP7 in chronic stress exposure through the binding of CB1 receptors. Adult male FABP7 and FABP7 mice were treated with the unpredictable chronic mild stress (UCMS) procedure.
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