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.
Highlights
Considerable immune activation is observed in the brain following the use of either alcohol or 3,4-Methylenedioxymethamphetamine (MDMA) [1,2,3,4,5], and the relationship between neuroinflammation and mood disorders is well recognized
We did not observe microglia activation in any of the drug groups compared to controls, we did detect a significantly increased number of ionized calcium binding adaptor molecule 1 (Iba1)+ cells/mm2 in animals that consumed EtOH compared to those that consumed MDMA (Fig 2E, 2H and 2K); there was no difference between the dorsal and ventral hippocampus
This work underlines the influence of two common recreational drugs, EtOH and MDMA, on performance in a contextual fear discrimination task, a feature related to hippocampal activity, which may be related to impairments observed in patients with anxiety-related disorders [25]
Summary
Considerable immune activation is observed in the brain following the use of either alcohol or 3,4-Methylenedioxymethamphetamine (MDMA) [1,2,3,4,5], and the relationship between neuroinflammation and mood disorders is well recognized (for review see [6,7]). High-risk consumption, or binge drinking, is common among teenagers throughout Europe and the US [8] and alcohol is frequently consumed together with other drugs of abuse, psychostimulants like MDMA/“Ecstasy” [9,10,11]. The effects of both drugs on emotions are well documented (for review see [12,13,14]). Patients with panic disorder, a specific subgroup of anxietyrelated disorders, show alterations in both the neurotrophic factor and IL-1β [23,24]
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