Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

The present study indicates that previous EtOH consumption as well as stress exposure induces increased EtOH conditioning, which can be related to dopaminergic alterations in the PFC or NAc. Interestingly, concomitant exposure to both stimuli abolished each other's effect on conditioning and PFC or NAc alterations. This protective outcome can be related to the dopaminergic increase in the amygdala.

Stress and ethanol consumption are known to affect the immune system, interfering in individual health, and resistance to opportunistic diseases. When experienced together, stress and ethanol seem to interact uniquely, altering each other effects depending on the exposure schedule. However, the effects of social stress on chronic ethanol exposure effects on the immune system are not well elucidated.To study this interaction, we chronically treated male swiss mice with ethanol after repeated social defeat stress (SDS) exposure. Some animals were tested in the elevated plus-maze (EPM) and open field (OF) while another cohort had plasmatic TNF-α, TGF-β1, CXCL-1, CCL-2, and VEGF quantified. Mice exposed to SDS or ethanol withdrawal showed increased anxiety-like behaviors in the EPM, while ethanol withdrawal decreased locomotor activity. Both alterations were attenuated in the groups exposed to SDS and ethanol withdrawal. Ethanol and stress alone increased plasmatic CXCL-1, while only stress affected CCL-2 and VEGF. Our results suggest that SDS exposure and ethanol withdrawal attenuated the increase in anxietylike behaviors, but did not alter each other effects on cytokine content.