Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice

• Published in: PloS one Vol. 10; no. 11; p. e0142978
• Main Authors: Johansson, Emily M, García-Gutiérrez, María S, Moscoso-Castro, María, Manzanares, Jorge, Valverde, Olga
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.11.2015; Public Library of Science (PLoS)
• Subjects: Alcohol; Alcohol Drinking; Alcohol use; Alcoholic beverages; Animals; Anxiety; Anxiety - drug therapy; Behavior; Behavior, Animal - drug effects; Biomedical research; Brain; Brain research; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cognition - drug effects; Cognitive ability; Cytokines; Discrimination; Discrimination Learning - drug effects; Disorders; Drinking (Alcoholic beverages); Drogues; Drug abuse; Drug dosages; Drugs; Ecstasy (Drug); Efectes secundaris; Fear; Fear - drug effects; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Hallucinogens - adverse effects; Health aspects; Hippocampus; Hippocampus - drug effects; IL-1β; Immune response; Immunohistochemistry; Immunosuppressive agents; In vivo methods and tests; Inflammation; Interleukin-1beta - metabolism; Interleukins; Male; Maze Learning; MDMA; Medical research; Memory; Mice; Motor Activity - drug effects; N-Methyl-3,4-methylenedioxyamphetamine - adverse effects; Neurobiology; Neurogenesis; Neurons - drug effects; Neurosciences; Panic attacks; Polymerase Chain Reaction; Rates (Animals de laboratori); Rodents; Street Drugs - chemistry; United States; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0142978

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.