Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 Â 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders.
The lateral hypothalamic area (LHA) has two major roles: arousal/waking and food intake controls. Here, it is shown that a premammillary part of the LHA is neurochemically and cytoarchitectonically distinct from the tuberal LHA in male rats. This part contains nuclear masses, namely the parasubthalamic nucleus and the calbindin nucleus, involved in pathways that predict its participation in the control of food intake. Analyzing c-Fos expression in experiments related to feeding behavior, this region responded specifically to the ingestion of palatable nutriments.
Transcranial direct current stimulation (tDCS) is a non-invasive method to modulate cortical excitability. This technique is a promising emerging tool to treat several neuropathologies, including addiction. We have previously shown in mice that repeated tDCS normalizes pathological behaviors associated with chronic nicotine exposure. Here, we evaluated, in adult female mice, the impact of tDCS on cocaine-induced behavior and gene regulation in corticostriatal circuits implicated in psychostimulant addiction. Anodal tDCS was applied transcranially over the frontal cortex. Three weeks after repeated tDCS, we investigated the induction of a gene expression marker (Zif268) by cocaine (25 mg/kg) in 26 cortical and 23 striatal regions using in situ hybridization histochemistry. We also assessed place preference conditioning by cocaine (5, 10, and 25 mg/kg). tDCS pretreatment increased basal expression and attenuated cocaine (25 mg/kg)-induced expression of Zif268 in specific corticostriatal circuits. Cocaine-induced locomotor activation (25 mg/kg) and place preference conditioning (5 and 25 mg/kg) were also reduced. These results demonstrate that tDCS can attenuate molecular and behavioral responses to cocaine for several weeks. Together, our findings provide pre-clinical evidence that such electrical brain stimulation may be useful to modify the psychostimulant addiction risk.
Non-invasive neuromodulatory techniques, including transcranial direct current stimulation (tDCS), have been shown to modulate neuronal function and are used both in cognitive neuroscience and to treat neuropsychiatric conditions. In this context, animal models provide a powerful tool to identify the neurobiological mechanisms of action of tDCS. However, finding a current generator that is easily usable and which allows a wide range of stimulation parameters can be difficult and/or expensive. Here, we introduce the Open-tES device, a project under a Creative Commons License (CC BY, SA 4.0) shared on the collaborative platform Git-Hub. This current generator allows tDCS (and other kinds of stimulations) to be realized, is suitable for rodents, is easy to use, and is low-cost. Characterization has been performed to measure the precision and accuracy of the current delivered. We also aimed to compare its effects with a commercial stimulator used in clinical trials (DC-Stimulator Plus, NeuroConn, Germany). To achieve this, a behavioral study was conducted to evaluate its efficacy for decreasing depression related-behavior in mice. The stimulator precision and accuracy were better than 250 nA and 25 nA, respectively. The behavioral evaluation performed in mice in the present study did not reveal any significant differences between the commercial stimulator used in clinical trials and the Open-tES device. Accuracy and precision of the stimulator ensure high repeatability of the stimulations. This current generator constitutes a reliable and inexpensive tool that is useful for preclinical studies in the field of non-invasive electrical brain stimulation.
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