title: Interaction between interleukin-1β and type-1 cannabinoid receptor is involved in anxiety-like behavior in experimental autoimmune encephalomyelitis.
abstract: Mood disorders, including anxiety and depression, are frequently diagnosed in multiple sclerosis (MS) patients, even independently of the disabling symptoms associated with the disease. Anatomical, biochemical, and pharmacological evidence indicates that type-1 cannabinoid receptor (CB1R) is implicated in the control of emotional behavior and is modulated during inflammatory neurodegenerative diseases such as MS and experimental autoimmune encephalomyelitis (EAE).
  
  
  
  We investigated whether CB1R could exert a role in anxiety-like behavior in mice with EAE. We performed behavioral, pharmacological, and electrophysiological experiments to explore the link between central inflammation, mood, and CB1R function in EAE.
  
  
  
  We observed that EAE-induced anxiety was associated with the downregulation of CB1R-mediated control of striatal GABA synaptic transmission and was exacerbated in mice lacking CB1R (CB1R-KO mice). Central blockade of interleukin-1β (IL-1β) reversed the anxiety-like phenotype of EAE mice, an effect associated with the concomitant rescue of dopamine (DA)-regulated spontaneous behavior, and DA-CB1R neurotransmission, leading to the rescue of striatal CB1R sensitivity.
  
  
  
  Overall, results of the present investigation indicate that synaptic dysfunction linked to CB1R is involved in EAE-related anxiety and motivation-based behavior and contribute to clarify the complex neurobiological mechanisms underlying mood disorders associated to MS.
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.
authors: Antonietta
authors: A
authors: Gentile
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.
authors: Diego
authors: D
authors: Fresegna
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.
authors: Alessandra
authors: A
authors: Musella
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.
authors: Helena
authors: H
authors: Sepman
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.
authors: Silvia
authors: S
authors: Bullitta
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.
authors: Francesca
authors: F
authors: De Vito
authors: Unit of Neurology and of Neurorehabilitation, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077, Pozzilli, IS, Italy.
authors: Roberta
authors: R
authors: Fantozzi
authors: Behavioural Neuroscience Laboratory, CEINGE Biotecnologie Avanzate, 80145, Naples, Italy.|Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples (SUN), Caserta, Italy.
authors: Alessandro
authors: A
authors: Usiello
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Centro di Ricerca Integrata, Facoltà di Medicina e Chirurgia, Università Campus Bio-Medico, 00128, Rome, Italy.
authors: Mauro
authors: M
authors: Maccarrone
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy.|Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.
authors: Nicola B
authors: NB
authors: Mercuri
authors: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128, Mainz, Germany.
authors: Beat
authors: B
authors: Lutz
authors: Laboratory of Neuroimmunology and Synaptic Transmission, IRCCS Fondazione Santa Lucia, Centro Europeo di Ricerca sul Cervello (CERC), 00143, Rome, Italy. g.mandolesi@hsantalucia.it.
authors: Georgia
authors: G
authors: Mandolesi
authors: Department of Systems Medicine, Tor Vergata University, 00133, Rome, Italy.|Unit of Neurology and of Neurorehabilitation, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077, Pozzilli, IS, Italy.
authors: Diego
authors: D
authors: Centonze
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003623:Dark Adaptation / Q000187:drug effects; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018501:Antirheumatic Agents; D000697:Central Nervous System Stimulants; C543264:Cnr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D043884:Receptor, Cannabinoid, CB1; C445081:myelin oligodendrocyte glycoprotein (35-55); D000661:Amphetamine
keywords: Anxiety; Experimental autoimmune encephalomyelitis; Interleukin-1β; Striatum; Type-1 cannabinoid receptor