Search results for " CB1"
showing 10 items of 111 documents
Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors
2007
Although endocannabinoids constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting from the central actions of cannabinoids. We deleted the type 1 cannabinoid receptor (CB1) specifically in nociceptive neurons localized in the peripheral nervous system of mice, preserving its expression in the CNS, and analyzed these genetically modified mice in preclinical models of inflammatory and neuropathic pain. The nociceptor-spec…
Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists
2014
The purpose of this study was the generation of central nervous system (CNS)-excluded cannabinoid receptor agonists to test the hypothesis that inhibition of spasticity, due to CNS autoimmunity, could be controlled by affecting neurotransmission within the periphery. Procedures included identification of chemicals and modeling to predict the mode of exclusion; induction and control of spasticity in the ABH mouse model of multiple sclerosis; conditional deletion of CB1 receptor in peripheral nerves; side-effect profiling to demonstrate the mechanism of CNS-exclusion via drug pumps; genome-wide association study in N2(129×ABH) backcross to map polymorphic cannabinoid drug pump; and sequencing…
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.
2007
The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity. We found that CB(1) receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB(2) receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB(2)-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher…
AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.
2010
The CB1 cannabinoid receptor is the most abundant G-protein coupled receptor in the brain and a key regulator of neuronal excitability. There is strong evidence that CB1 receptor on glutamatergic hippocampal neurons is beneficial to alleviate epileptiform seizures in mouse and man. Therefore, we hypothesized that experimentally increased CB1 gene dosage in principal neurons would have therapeutic effects in kainic acid (KA)-induced hippocampal pathogenesis. Here, we show that virus-mediated conditional overexpression of CB1 receptor in pyramidal and mossy cells of the hippocampus is neuroprotective and moderates convulsions in the acute KA seizure model in mice. We introduce a recombinant a…
Pre- and postsynaptic type-1 cannabinoid receptors control the alterations of glutamate transmission in experimental autoimmune encephalomyelitis
2013
Type-1 cannabinoid receptors (CB1R) are important regulators of the neurodegenerative damage in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). In GABAergic striatal neurons, CB1R stimulation exerts protective effects by limiting inflammation-induced potentiation of glutamate-mediated spontaneous excitatory postsynaptic currents (sEPSCs). Here we show that CB1R located on GABAergic or on glutamatergic neurons are differentially involved in the pre- and postsynaptic alterations of sEPSCs caused by EAE in the striatum. After induction of EAE, mice selectively lacking CB1R on GABAergic neurons (GABA-CB1R-KO) showed exacerbated alterations of sEPSC duration in GA…
Identification of the cannabinoid receptor type 1 in serotonergic cells of raphe nuclei in mice.
2007
The endocannabinoid system (ECS) possesses neuromodulatory functions by influencing the release of various neurotransmitters, including GABA, noradrenaline, dopamine, glutamate and acetylcholine. Even though there are studies indicating similar interactions between the ECS and the serotonergic system, there are no results showing clear evidence for type 1 cannabinoid receptor (CB1) location on serotonergic neurons. In this study, we show by in situ hybridization that a low but significant fraction of serotonergic neurons in the raphe nuclei of mice contains CB1 mRNA as illustrated by the coexpression with the serotonergic marker gene tryptophane hydroxylase 2, the rate limiting enzyme for t…
The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance
2005
During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expr…
Cannabinoid 1 Receptors in Keratinocytes Modulate Proinflammatory Chemokine Secretion and Attenuate Contact Allergic Inflammation
2013
Abstract Epidermal keratinocytes (KCs) and cannabinoid (CB) receptors both participate in the regulation of inflammatory responses in a mouse model for allergic contact dermatitis, the contact hypersensitivity (CHS) response to the obligate sensitizer 2,4-dinitrofluorobenzene. In this study, we investigated the cellular and molecular mechanisms how CB1 receptors attenuate CHS responses to 2,4-dinitrofluorobenzene. We used a conditional gene-targeting approach to identify the relative contribution of CB1 receptors on epidermal KCs for the control of CHS responses. To determine the underlying cellular and molecular mechanisms that regulate inflammatory responses in the effector phase of CHS, …
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…