Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice

Emily M. Johansson, María S. García-Gutiérrez, María Moscoso-Castro, Jorge Manzanares, Olga Valverde
PLoS ONE. 2015-11-13; 10(11): e0142978
DOI: 10.1371/journal.pone.0142978

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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.


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