INTERLEUKIN-1β ALTERS THE SENSITIVITY OF CANNABINOID CB1 RECEPTORS CONTROLLING GLUTAMATE TRANSMISSION IN THE STRIATUM

Proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta (IL1 beta) regulate both excitatory and inhibitory synaptic transmission in the central nervous system. The interaction between IL1 beta and endocannabinoid system (ECS) is also emerging, based on the evidence that IL1 beta effects on striatal spontaneous excitatory and inhibitory postsynaptic currents are regulated by transient receptor potential vanilloid 1 (TRPV1) channels, members of the ECS. 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 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.