Research Article: Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice

Date Published: January 20, 2017

Publisher: Public Library of Science

Author(s): Priscila Marianno, Karina Possa Abrahao, Rosana Camarini, Andrey E Ryabinin.


Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE) affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h) or continuous (24 h) EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress) to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase). Control mice were housed under standard conditions (SC). In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h). In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h). After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM) during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress.

Partial Text

Alcohol addiction is a complex psychiatric disorder strongly influenced by environmental factors [1]. Animal models can mimic one or more aspects of addiction. Attention has been given to animal models that can elicit high levels of alcohol consumption and preference [2]. High ethanol intake, in which the animal may overcome the initial aversive taste of ethanol and drink sufficient quantities to achieve a state of intoxication [3], can be evaluated in self-administration models. In one such model, two bottles are presented to the animals: one containing tap water and another containing an alcohol solution [4]. Previous studies have shown that alcohol consumption in the two-bottle choice paradigm can be further increased after periods of ethanol deprivation [5, 6, 7, 8], which may mimic some aspects of repeated withdrawals, persistent craving and relapse in humans [9]. This phenomenon is called alcohol deprivation effect (ADE). In these experimental models, inbred C57BL/6 mice have been widely used because they present a predisposition to voluntarily consume significant quantities of alcohol to the point of behavioral intoxication [10].

The present study showed that continuous, but not intermittent, EE increased anxiety-like behavior in mice. In addition, restraint stress decreased ethanol consumption during the first 2 h access to the 2-bottle choice regardless the environmental condition. However, mice living in a continuous EE (24 h/day) or restricted EE (3 h/day) consumed less alcohol over a 24 h period after an acute stressful stimulus compared to mice living in a standard condition.




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