Abstract
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.
Highlights
Alcohol addiction is a complex psychiatric disorder strongly influenced by environmental factors [1]
The results revealed mean blood ethanol concentrations (BECs) of 1.79 ± 0.10 mg/ml and mean ethanol consumption of 3.41 ± 0.47 g/kg, which are consistent with intoxicating levels
A significant positive correlation was found between the levels of ethanol intake and BECs (r2 = 0.41, p < 0.05; Fig 2B)
Summary
Alcohol addiction is a complex psychiatric disorder strongly influenced by environmental factors [1]. 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). We evaluated whether short (3 h) or continuous (24 h) exposure to EE affect ethanol consumption after repeated withdrawal cycles and after an acute stress situation
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