title: Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice.
abstract: The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders.
authors.affiliation: Neurobiology of Behaviour Research Group (GReNeC), Department of Health and Experimental Sciences, Universitat Pompeu Fabra, IMIM, Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park C/Dr. Aiguader 88, 08003, Barcelona, Spain.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Johansson
authors.affiliation: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Avda. Ramón y Cajal s/n, San Juan de Alicante, Alicante, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: María S
authors.initials: MS
authors.lastname: García-Gutiérrez
authors.affiliation: Neurobiology of Behaviour Research Group (GReNeC), Department of Health and Experimental Sciences, Universitat Pompeu Fabra, IMIM, Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park C/Dr. Aiguader 88, 08003, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Moscoso-Castro
authors.affiliation: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Avda. Ramón y Cajal s/n, San Juan de Alicante, Alicante, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
authors.affiliation: Neurobiology of Behaviour Research Group (GReNeC), Department of Health and Experimental Sciences, Universitat Pompeu Fabra, IMIM, Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park C/Dr. Aiguader 88, 08003, Barcelona, Spain.|Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Valverde
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D005239:Fear / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006213:Hallucinogens / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects; D013287:Illicit Drugs / Q000737:chemistry; D007150:Immunohistochemistry; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D018782:Maze Learning; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D009474:Neurons / Q000187:drug effects; D016133:Polymerase Chain Reaction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006213:Hallucinogens; C587672:IL1B protein, mouse; D013287:Illicit Drugs; D053583:Interleukin-1beta; D018817:N-Methyl-3,4-methylenedioxyamphetamine