Furthermore, IL1 beta has also been shown to control the sensitivity of cannabinoid CB1 receptors controlling GABA transmission (CB1RS((GABA))) in the striatum. To better detail the synaptic action of IL1 beta, and to clarify its complex interaction with the ECS, here we investigated the possible interplay between IL1 beta and CB1Rs controlling glutamate transmission (CB1Rs((glu))), other critical elements of the ECS. Our results show that the sensitivity of CB1Rs((glu)) is fully blocked in the presence of IL1 beta in corticostriatal EPZ-6438 chemical structure brain slices, and that the protein kinase C/TRPV1 pathway is involved in this effect. IL1

beta failed to modulate the sensitivity of glutamate synapses to the stimulation of GABAB receptors. We also provided evidence that IL1 beta-CB1RS((GABA)) but not IL1 beta-CB1Rs((glu)) interaction is under the control of the brain-derived neurotrophic factor (BDNF)/trkB signaling and of lipid raft composition, because BDNF gene partial deletion, pharmacological blockade of trkB and membrane cholesterol removal with methyl-beta-cyclodextrin all blocked

IL1 beta-mediated inhibition of CB1Rs((GABA)) but left unaltered the sensitivity of CB1Rs((glu)) to this cytokine. Our results provide further evidence that synaptic transmission and the ECS are regulated by IL1 beta in the striatum. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Contrary selleckchem to the reduction of depressive-like behavior observed in several strains of cytokine receptor knockout mice, mice lacking the specific receptor I-BET-762 supplier for interleukin (IL)-15 showed increased immobility in tail suspension and modified forced

swimming tests. There was also a reduction in social interactions. The hippocampus of the IL15R alpha knockout mice had decreased mRNA for 5-HT(1A), increased mRNA for 5-HT(2c), and region-specific changes of serotonin reuptake transporter (SERT) immunoreactivity. Fluoxetine (the classic antidepressant Prozac, which inhibits 5-HT(2c) and SERT) reduced the immobility of the IL15R alpha knockout mice in comparison with their pretreatment baseline. Together with the unchanged performance of the IL15R alpha knockout mice on the rotarod, this response to fluoxetine indicates that the immobility reflects depression. Wildtype mice responded to IL15 treatment with improvement of immobility induced by forced swimming, whereas the knockout mice failed to respond. Thus, the cognate IL15 receptor is necessary for the antidepressive activity of IL15. In ex vivo studies, IL15 decreased synaptosomal uptake of 5-HT, and modulated the expression of 5-HT(2c) and SERT in cultured neurons in a dose- and time-dependent manner. Thus, the effect of 1L15 on serotonin transmission may underlie the depressive-like behavior of IL15R alpha knockout mice.