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

Abstract

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 selfadministerethanol 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.

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

“…Our data showed that, in contrast to findings with nicotine 43 and cocaine 44 , tDCS did not modulate the hedonic effect of ethanol assessed in the place preference paradigm, a test that combines Pavlovian conditioning and testing in a drug-free state. Furthermore, tDCS also did not modulate the expression of ethanol-induced behavioral sensitization, which has previously been linked to high ethanol intake in operant procedures 49 . In contrast, tDCS robustly reduced the reacquisition of ethanol consumption (50% decrease) following extinction in an operant paradigm.…”

“…Behavioral sensitization is defined as a progressive and long-lasting increase in specific behaviors after repeated drug exposure, with the most studied behavior being locomotion. A recent study showed that in mice, sensitization to the motor stimulant effects of ethanol was associated with facilitation of the acquisition of ethanol self-administration in an operant task 49 . It was therefore of interest to evaluate the impact of tDCS on ethanol-induced behavioral sensitization.…”

“…In the first experiment, we used the place preference conditioning paradigm to evaluate the impact of tDCS on the hedonic effect of ethanol (“Do I like it?”). In a second experiment, we evaluated the effects of tDCS on the expression of ethanol-induced behavioral sensitization, which has been hypothesized to reflect drug-induced long-term neuroplasticity in the nucleus accumbens 49 . In these experiments, ethanol was passively administered, i.e., intraperitoneally administered by the experimenter.…”

Interstrain differences in voluntary binge‐like drinking behavior and in two acute ethanol injections‐induced synaptic plasticity deficits in rats

“…28 The vast majority of studies on operant ethanol self-administration in rodents has been carried out in rats, and only very few studies have been published in mice. 29 Rats have been suggested to be the smart choice for studies on behavioral genetics and particularly in the addiction field. 30 We recently proposed a new procedure in outbred rats to mimic BD behavior, and we demonstrated that our model displays good face validity and predictive validity.…”

“…Most of the studies on voluntary BD in rodents are using the drinking‐in‐the‐dark model in inbred mice 28 . The vast majority of studies on operant ethanol self‐administration in rodents has been carried out in rats, and only very few studies have been published in mice 29 . Rats have been suggested to be the smart choice for studies on behavioral genetics and particularly in the addiction field 30 .…”