Transcranial direct current stimulation (tDCS) reduces motivation to drink ethanol and reacquisition of ethanol self-administration in female mice

Abstract

Transcranial direct current stimulation (tDCS) is an emerging noninvasive brain neuromodulation technique aimed at relieving symptoms associated with psychiatric disorders, including addiction. The goal of the present study was to better identify which phase of alcohol-related behavior (hedonic effect, behavioral sensitization, self-administration, or motivation to obtain the drug) might be modulated by repeated anodal tDCS over the frontal cortex (0.2 mA, 20 min, twice a day for 5 consecutive days), using female mice as a model. Our data showed that tDCS did not modulate the hedonic effects of ethanol as assessed by a conditioned place preference test (CPP) or the expression of ethanol-induced behavioral sensitization. Interestingly, tDCS robustly reduced reacquisition of ethanol consumption (50% decrease) following extinction of self-administration in an operant paradigm. Furthermore, tDCS significantly decreased motivation to drink ethanol on a progressive ratio schedule (30% decrease). Taken together, our results show a dissociation between the effects of tDCS on “liking” (hedonic aspect; no effect in the CPP) and “wanting” (motivation; decreased consumption on a progressive ratio schedule). Our tDCS procedure in rodents will allow us to better understand its mechanisms of action in order to accelerate its use as a complementary and innovative tool to help alcohol-dependent patients maintain abstinence or reduce ethanol intake.

Repeated Anodal Transcranial Direct Current Stimulation (RA-tDCS) over the Left Frontal Lobe Increases Bilateral Hippocampal Cell Proliferation in Young Adult but Not Middle-Aged Female Mice

“…A constant current of 0.2 mA was applied transcranially in two sessions of 20 min per day for five consecutive days, with a linear fade-in and fade-out of 10 s, using a direct current stimulator (DC-Stimulator Plus) or an Open-tES stimulator (d) [31]. Adapted from Pedron et al (2022) [32].…”

“…One week before starting the stimulation protocol, a tubular plastic electrode holder (internal diameter 2.1 mm; DIXI Medical, Besançon, France; Figure 5C) was surgically affixed to each mouse's skull, as previously described [27][28][29][30][31][32]. Briefly, the animals were anesthetized with ketamine hydrochloride/xylazine (80/12 mg/kg, intraperitoneal [i.p.]…”

“…A custommade restraining box was used to hold a larger rectangular rubber-plate electrode (cathode, 9.5 cm 2 ; Physiomed Elektromedizin AG, Schnaittach, Germany; Figure 5E,F) against the ventral thorax, as previously described [29]. The animals were stimulated for five consecutive days (2 × 20 min/day; 5 h interstimulation interval [29,30,32]; linear fade-in and fade-out; 10 s ramp [27]), with an anodal constant current (0.2 mA) using a DC-Stimulator Plus (NeuroConn, Illmenau, Germany) or an Open-tES stimulator specifically designed for rodent research [31]. The control (Sham) animals were subjected to the same procedure (surgery, restraining box, and electrode fixation) but no current was delivered.…”

“…However, the mechanisms underlying its effects remain poorly understood. In an effort to better identify the neurobiological processes involved, we have previously set up a tDCS protocol that can be used in mice [27][28][29][30][31][32][33]. We have shown that repeated sessions of anodal tDCS (RA-tDCS) have AD-like properties in naïve [29] and in depressed (i.e., in CORT-treated) [28] young adult mice and significantly improve working memory in naïve young adult mice [29].…”

Frontal tDCS reduces alcohol relapse rates by increasing connections from left dorsolateral prefrontal cortex to addiction networks

“…Preclinical and clinical studies suggest DLPFC stimulation is a promising intervention target for neuromodulation trials in substance use disorder. Preclinical research has reported reduced motivation to consume alcohol, reduced alcohol consumption and reduced reacquisition of ethanol consumption after multiple sessions of transcranial direct current stimulation (tDCS) to the frontal cortex in murine models [17,18]. Clinical studies have reported reduced craving and risk of relapse after multiple sessions (five [2,3] or ten sessions [19]) of DLPFC stimulation.…”