title: Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.
abstract: Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.
authors.affiliation: Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain; Endocannabinoids and Neuroadaptation Group, NeuroCentre Magendie, INSERM U1215, 33077, Bordeaux, France;
authors.forename: Arnau
authors.initials: A
authors.lastname: Busquets-Garcia
authors.affiliation: Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;
authors.forename: Maria
authors.initials: M
authors.lastname: Gomis-González
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
authors.forename: Raj Kamal
authors.initials: RK
authors.lastname: Srivastava
authors.affiliation: Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;
authors.forename: Laura
authors.initials: L
authors.lastname: Cutando
authors.affiliation: Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;
authors.forename: Antonio
authors.initials: A
authors.lastname: Ortega-Alvaro
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ruehle
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
authors.forename: Floortje
authors.initials: F
authors.lastname: Remmers
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Bindila
authors.affiliation: Endocannabinoids and Neuroadaptation Group, NeuroCentre Magendie, INSERM U1215, 33077, Bordeaux, France;
authors.forename: Luigi
authors.initials: L
authors.lastname: Bellocchio
authors.affiliation: Endocannabinoids and Neuroadaptation Group, NeuroCentre Magendie, INSERM U1215, 33077, Bordeaux, France;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.affiliation: Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.affiliation: Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain; andres.ozaita@upf.edu.
authors.forename: Andrés
authors.identifier: 0000-0002-2239-7403
authors.initials: A
authors.lastname: Ozaita
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004597:Electroshock / Q000009:adverse effects; D019417:Hindlimb Suspension / Q000009:adverse effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000077285:Rimonabant; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology*
chemical_list: D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000841:Anisomycin; D004299:Dopamine beta-Hydroxylase; D000077285:Rimonabant; C094023:iodopravadoline
keywords: cannabinoid receptor; endocannabinoid system; memory consolidation; noradrenergic signaling; stress response