Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice

Abstract

The rewarding effects of alcohol can lead to progressively heavier and more frequent drinking. Since studies of reward have mainly focused on responses to higher alcohol doses, the relations between reward and moderate/sustained alcohol exposure remain unknown. Our objective was to evaluate factors affecting the reward value of low alcohol doses and risk factors for increasing alcohol doses due to reward progression caused by alcohol exposure patterns. We thus performed conditioned place preference (CPP) and ethanol (EtOH)-induced locomotor sensitization tests in mice. Low-dose EtOH (0.5 or 1 g/kg twice/week)-induced CPP was stronger than that produced by saline control treatment, but the effect decreased with increasing numbers of conditioning trials. Moderate-dose/long-term EtOH exposure induced a weaker CPP than high-dose/short-term EtOH (2 g/kg twice/week) exposure with the same total EtOH dose (8 g/kg/experiment). Acamprosate calcium, an anti-relapse drug, preclusively reduced EtOH-induced CPP. EtOH induced CPP and locomotor sensitization in black but not white chamber, although the initial preference and the basal locomotion in each chamber were equal. Therefore the brightness of the chamber had an effect on EtOHinduced sensitization. Moreover, additional studies indicated that EtOH-induced locomotor sensitization also depends on the dose but not the administration interval. Paired associative learning with EtOH exposure is a potent factor influencing the level of reward produced by EtOH. Moreover, exposure to high doses of alcohol, even on an intermittent schedule, carries a higher risk of addiction than exposure to moderate doses over longer periods.Key words moderate alcohol (ethanol: EtOH); conditioned place preference (CPP); reward; sensitization; paired associative learning Alcohol abuse is associated with serious physical and psychiatric illnesses, financial hardships, familial dysfunction, and violence, all of which place a substantial burden on society. Heavy alcohol consumption and long-term drinking increase the risk of alcohol-related diseases such as liver cirrhosis, cancer, pancreatitis, and depression. 1,2) In response, the World Health Organization (WHO) recently approved a Global Strategy to Reduce Harmful Use of Alcohol urging all countries to strengthen national responses to public health problems caused by alcohol use.3) In Japan, 6.45 million people suffer from alcohol-related problems, with an estimated annual economic loss of 4.15 trillion yen associated with alcohol. 4) In December 2013, the Basic Act on Measures against Alcohol-related Health Harm was enacted in Japan, promoting education about drinking in moderation to prevent alcoholrelated problems.Regular consumption of alcohol increases the propensity for addiction because of the rewarding effects of alcohol. Thus, many casual drinkers gradually increase total alcohol consumption, which becomes habitual over time. Although many studies in rodents have been conducted on chronic drinking and reward, 5-7) previous studies have ma...

Moderate-dose Regular Lifelong Alcohol Intake Changes the Intestinal Flora, Protects against Aging, and Keeps Spatial Memory in the Senescence-accelerated Mouse Prone 8 (SAMP8) Model

“…We previously reported the relationship between moderate EtOH intake and reward assessed by using conditioned place preference (CPP) test and locomotor sensitization in DBA/2 CrSlc mice. We found that moderate, but long-term, EtOH dose may confer a lower risk for reward progression than the high dose for shorter periods (17). The results of this study supported the low risk of reward by low alcohol, although the oral intake in this experiment was different from i.p.…”

“…The results of this study supported the low risk of reward by low alcohol, although the oral intake in this experiment was different from i.p. administration in the previous report (17). The consumption of 1% EtOH in place of water did not affect blood sugar levels at the age of 71-75 weeks or lifelong food consumption ( Figure 2B).…”

Social and environmental enrichment has different effects on ethanol and sucrose consumption in mice

“…In each of these studies, rehousing ethanolexperienced rats in a social setting produced an increase in ethanol consumption; whereas the former studies were performed in ethanolnaive animals. From previous rodent research, we know that changes to housing conditions are stressful for rodents (Misslin, Herzog, Koch, & Ropartz, 1982;Tuli, Smith, & Morton, 1995), rodents in an isolated housing environment are more sensitive to stress than those in a social environment (Giralt & Armario, 1989), stress alters ethanol consumption (Cozzoli, Tanchuck-Nipper, Kaufman, Horowitz, & Finn, 2014;Meyer, Long, Fanselow, & Spigelman, 2013), ethanol experience alters ethanol reward value (Shimizu et al, 2015;McCusker & Bell, 1988), and ethanol consumption reduces the ability to cope with stress (Zhao, Weiss, & Zorrilla, 2007). Taken together, one could argue that for ethanol-naïve rats, the provision of social interactions provides greater rewarding benefits/stress relief than the biological effects obtained from ethanol consumption.…”

“…As the mice in the previous experiment were naïve to ethanol and prior ethanol experience can alter the perceived reward value of ethanol (Shimizu, Oki, Mitani, Nakamura, & Nabeshima, 2015), we explored whether the biological effects of ethanol outweighed the effects of social and environmental enrichment in mice with previous ethanol experience. To achieve this, we provided enrichment to deprived mice and deprived enriched mice of social and environmental interactions.…”

Effects of Oral Calcium Dosage and Timing on Ethanol-Induced Sensitization of Locomotion in DBA/2 Mice

“…1) Disease burden is related to amount of alcohol consumption and drinking patterns (drinking frequency during the week and in relation to food consumption) 1,2) On the contrary, many epidemiological studies have also suggested that moderate alcohol consumption reduces the risk of mortality and of some diseases, such as cardiovascular diseases 3,4) and dementia. 5) Moderate drinking is implicated in health and QOL. For clarifying the influence of moderate alcohol consumption on health, we have reported the risk of reward by moderate-dose/ long-term EtOH administration 6) and the relation between moderate/sustained alcohol intake and health during the lifespan in rodents.…”