Search results for "Rimonabant"
showing 10 items of 31 documents
Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR- and BECLIN1-complex
2013
Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for Delta-9-Tetrahydrocannabinol in the central nervous system (CNS), mediating retrograde synaptic signaling of the endocannabinoid system. Beside its expression in various CNS regions, CB1 is ubiquituous in peripheral tissues, where it mediates, among other activities, the cell's energy homeostasis. We sought to examine the role of CB1 in the context of the evolutionarily conserved autophagic machinery, a main constituent of the regulation of the intracellular energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an elevated autophagic flux, while the expression of autophagy-related genes rema…
The Peptide Hemopressin Acts through CB1Cannabinoid Receptors to Reduce Food Intake in Rats and Mice
2010
Hemopressin is a short, nine amino acid peptide (H-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His-OH) isolated from rat brain that behaves as an inverse agonist at the cannabinoid receptor CB1, and is shown here to inhibit agonist-induced receptor internalization in a heterologous cell model. Since this peptide occurs naturally in the rodent brain, we determined its effect on appetite, an established central target of cannabinoid signaling. Hemopressin dose-dependently decreases night-time food intake in normal male rats and mice, as well as in obeseob/obmale mice, when administered centrally or systemically, without causing any obvious adverse side effects. The normal, behavioral satiety sequence is …
Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice.
2012
Cannabinoid type 1 (CB(1)) receptor activation is generally considered a powerful orexigenic signal and inhibition of the endocannabinoid system is beneficial for the treatment of obesity and related metabolic diseases. The hypothalamus plays a critical role in regulating energy balance by modulating both food intake and energy expenditure. Although CB(1) receptor signaling has been implicated in the modulation of both these mechanisms, a complete understanding of its role in the hypothalamus is still lacking. Here we combined a genetic approach with the use of adeno-associated viral vectors to delete the CB(1) receptor gene in the adult mouse hypothalamus and assessed the impact of such ma…
How many sites of action for endocannabinoids to control energy metabolism?
2006
The promising results obtained by clinical trials using Rimonabant to tackle visceral obesity and related disorders recently promoted a remarkable impulse to carry out detailed investigations into the mechanisms of action of endocannabinoids in regulating food intake and energy metabolism. The endocannabinoid system has been known for many years to play an important role in the modulation of the neuronal pathways mediating the rewarding properties of food. However, in the last few years, with the advanced understanding of the crucial role of the hypothalamic neuronal network in the regulation of appetite, several studies have also directed attention to the orexigenic role of the endocannabi…
Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice
2010
AbstractBackgroundNumerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice.MethodsIn the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, r…
Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (r)-(+)-[2,3-dihydro-5-methyl-3-(4-m…
2003
The aim of the present in vivo microdialysis study was to investigate whether prenatal exposure to the CB1 receptor agonist WIN55,212-2 mesylate (WIN; (R)-()-(2,3- dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo(1,2,3-de)- 1,4-benzoxazin-6-yl)-1-naphthalenylmethanone), at a dose of 0.5 mg/kg (s.c. from the fifth to the 20th day of gestation), that causes neither malformations nor overt signs of toxicity, influences cortical glutamate extracellular levels in adult (90- day old) rats. Dam weight gain, pregnancy length and litter size at birth were not significantly affected by prenatal treatment with WIN. Basal and K-evoked dialysate glutamate levels were lower in the cerebral cortex of adul…
Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations.
2007
Abstract While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomach was recorded and mechanical responses induced by ele…
Protective activation of the endocannabinoid system during ischemia in dopamine neurons
2006
Endocannabinoids act as neuroprotective molecules promptly released in response to pathological stimuli. Hence, they may represent one component of protection and/or repair mechanisms mobilized by dopamine (DA) neurons under ischemia. Here, we show that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) plays a key role in protecting DA neurons from ischemia-induced altered spontaneous activity both in vitro and in vivo. Accordingly, neuroprotection can be elicited through moderate cannabinoid receptor type-1 (CB1) activation. Conversely, blockade of endocannabinoid actions through CB1 receptor antagonism worsens the outcome of transient ischemia on DA neuronal activity. These findings indi…
Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (…
2007
Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids (eCBs), are the endogenous agonists for the cannabinoid receptor type 1 (CB1). Several pieces of evidence support a role for eCBs in the attenuation of anxiety-related behaviours, although the precise mechanism has remained uncertain. The fatty acid amid hydrolase (FAAH), an enzyme responsible for the degradation of eCBs, has emerged as a promising target for anxiety-related disorders, since FAAH inhibitors are able to increase the levels of anandamide and thereby induce anxiolytic-like effects in rodents. The present study adopted both genetic and pharmacological approaches and tested the hypothesis that FAAH-deficient…
Genetic dissection of the role of cannabinoid type-1 receptors in the emotional consequences of repeated social stress in mice.
2012
International audience; The endocannabinoid system (ECS) tightly controls emotional responses to acute aversive stimuli. Repeated stress alters ECS activity but the role played by the ECS in the emotional consequences of repeated stress has not been investigated in detail. This study used social defeat stress, together with pharmacology and genetics to examine the role of cannabinoid type-1 (CB(1)) receptors on repeated stress-induced emotional alterations. Seven daily social defeat sessions increased water (but not food) intake, sucrose preference, anxiety, cued fear expression, and adrenal weight in C57BL/6N mice. The first and the last social stress sessions triggered immediate brain reg…