The effects of lithium chloride and cathodal/anodal transcranial direct current stimulation on conditional fear memory c
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ORIGINAL ARTICLE
The effects of lithium chloride and cathodal/anodal transcranial direct current stimulation on conditional fear memory changes and the level of p-mTOR/mTOR in PFC of male NMRI mice Mojgan Hamdami 1,2 & Solmaz Khalifeh 3 & Nida Jamali-Raeufy 1
&
Mohammad Nasehi 3
Received: 24 September 2020 / Accepted: 3 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Lithium chloride clinically used to treat mental diseases but it has some side effects like cognitive impairment, memory deficit. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is able to change neural activity and gene transcription in the brain. The aim of the study is to provide a conceptual theoretical framework based on behavioral and molecular effects of tDCS on memory changes induced by lithium in male mice. we applied Anodal-tDCS and Cathodal-tDCS over the left PFC for 3 consecutive days tDCS for 20 min with 2 mA after injection of different doses of lithium/saline.Trained in fear condition and finally the day after that tested their memory persistency factors (freezing-latency) and other behavior such as grooming and rearing percentage time in the fear conditioning. P-mTOR/mTOR was analyzed using western blotting. The results obtained from the preliminary analysis of behavioral fear memory showed that lithium had destructive effect in higher doses and decreased freezing percentage time. However, both cathodal and anodal tDCS significantly improved memory and increased PmTOR/mTOR level in the PFC. The results of this study indicate that cathodal and anodal tDCS upon the left prefrontal increased memory and reduced lithium side effects on memory consolidation and altered expression of plasticity-associated genes in the prefrontal cortex. Keywords Cathodal Tdcs . Anodal tDCS, lithium . Conditional fear memory . mTOR
Introduction Lithium salts (Lithium carbonate/chloride) have known as primary drugs to treat and prevent bipolar disorder (Anand et al. 2020; Hillert et al. 2014; Orre 2013). It is near wholly absorbed in the upper gastrointestinal tract and metabolized in total body water, then slowly entry into blood–brain barrier (BBB) and brain cells (Orre 2013). Whereas lithium has a narrow therapeutic window (O’Donnell and Gould 2007), it has some common side effects including fine hand tremor, nausea, diarrhoea, * Nida Jamali-Raeufy [email protected] 1
Department of Medical Physiology, Iran University of Medical Sciences, Tehran, Iran
2
Student Research Committee, Iran University of Medical Science, Tehran, Iran
3
Cognitive and Neuroscience Research Center, Amir-Almomenin Hospital, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
weight gain, hypothyroidism, and neuropathic diabetes (Trepiccione and Monster Christensen 2010). Several studies have reported that lithium reduced learning, memory capacity, and other cognitive speed processing in patient, which received lithium in compare with control subjects (Pachet a
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