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

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.

Vulnerability to ethanol sensitization predicts higher intake and motivation to self-administer ethanol: Proof of the incentive salience sensitization theory?

Ethanol-induced behavioral sensitization (EIBS) is thought to play a key role in addiction. However, whether EIBS is linked to an increase in the motivation to self-administerethanol in an operant paradigm has never been demonstrated, and thus, the motivational sensitization theory (increase in drug wanting) has not been yet confirmed. We investigated using the operant ethanol self-administrationparadigm if the motivation to self-administerethanol (breakpoint) is increased in female mice prone to develop EIBS. Outbred female Swiss mice were treated once a day with 2.5-g ethanol per kilogram during 10 days and challenged with the same dose of ethanol 7 days later. EIBS-pronegroup was characterized by a significant increase in locomotion between the challenge day and day 1. When the difference was not significant, mice were considered as the "EIBS-resistant"group. Mice were then trained to nose poke for a 20% ethanol solution reinforcer under a FR1 and then a FR-2schedule of reinforcement. Motivation was assessed more directly with a progressive ratio schedule. Our results show that there is a positive correlation between EIBS and both the level of intake and motivation. Interestingly, acquisition of ethanol self-administrationwas faster in sensitized mice that also display a quick and long-lastingincrease in ethanol intake together with a lack of effect of alcohol challenge on c-Fosexpression restricted to the dorsolateral striatum. These results further support that EIBS vulnerability is crucial in the development of addictive behaviors and suggest a potential link with habit learning processes.