Department of Psychology, Tufts University, Medford, MB, 02155, USA.
Department of Neuroscience, Tufts University, Boston, MA, 02111, USA.
Psychopharmacology (Berl). 2022 Oct;239(10):3287-3296. doi: 10.1007/s00213-022-06211-8. Epub 2022 Aug 16.
The attraction to alcohol can be greatly increased when it is consumed in a social context. While pro-social interactions can potentiate voluntary alcohol drinking under some conditions, aversive social experience (i.e., social stress) can similarly intensify alcohol consumption.
We sought to determine how exposure to different types of chronic social stress (i.e., intermittent episodes of social defeat or continuous social stress) influences alcohol consumption and the reinforcing effects of alcohol in mice with a history of drinking.
Separate cohorts of male C57BL/6J mice were exposed to either 10 days of continuous or intermittent social defeat stress. In experiment 1, mice were assigned to 20% w/v alcohol consumption in a two-bottle choice protocol both prior to and after exposure to social defeat stress. In a second experiment, mice engaged in an operant response sequence to gain access to alcohol wherein completion of a fixed interval (FI; 5 min) schedule was reinforced with continuous access to alcohol (fixed ratio; FR1) for up to 1.8 g/kg. Alcohol-reinforced responding and subsequent alcohol consumption were assessed daily for 4 weeks prior to the 10-day social stress exposure and for 6-week post-stress. Machine learning was implemented to standardize the analysis of defeat behaviors exhibited by the intruder mouse during confrontation with an attacking resident.
In mice with a prior history of alcohol drinking, intermittent episodes of social defeat stress produced a significant increase in 20% EtOH consumption in preference over concurrently available water. This increased intake persisted for at least 6 weeks after the final social stress experience. Intermittently stressed mice also accelerated their anticipatory responding during the fixed interval component of the operant response chain that was reinforced by alcohol. Neither unstressed controls nor mice exposed to continuous social stress exhibited significant increases in alcohol consumption and alcohol reinforcement.
Episodic social defeat stress promotes the seeking and consumption of alcohol, extending earlier work to alcohol-experienced mice. We hypothesize that intermittent access to alcohol and intermittent episodes of social stress are additive and share common sensitizing neural mechanisms that engender excessive alcohol consumption.
在社交环境中饮酒时，酒精的吸引力会大大增加。虽然在某些条件下，亲社会互动可以增强自愿饮酒，但负面的社交体验（即社交应激）同样可以加剧饮酒。
我们旨在确定不同类型的慢性社交应激（即间歇性社交挫败或持续社交应激）暴露如何影响有饮酒史的小鼠的酒精消费和酒精的强化作用。
将不同批次的雄性 C57BL/6J 小鼠暴露于连续或间歇性社交挫败应激中。在实验 1 中，在暴露于社交挫败应激之前和之后，将小鼠分配到 20% w/v 酒精的双瓶选择方案中进行消费。在第二个实验中，小鼠进行了一个操作性反应序列，以获得酒精的访问权限，其中完成固定间隔（FI；5 分钟）时间表的奖励是连续访问酒精（固定比率；FR1），最高可达 1.8 g/kg。在暴露于 10 天社交应激之前以及应激后 6 周，每天评估酒精强化反应和随后的酒精消费。实施机器学习以标准化入侵者在与攻击型居民对抗时表现出的挫败行为的分析。
在有饮酒史的小鼠中，间歇性社交挫败应激显著增加了对 20%乙醇的偏好性消费，超过了同时提供的水。这种增加的摄入量至少持续到最后一次社交应激体验后的 6 周。间歇性应激的小鼠还在通过酒精强化的操作性反应链的固定间隔成分中加速了他们的预期反应。未受应激的对照小鼠或暴露于持续社交应激的小鼠均未表现出显著的酒精消费和酒精强化增加。
间歇性社交挫败应激促进了对酒精的寻求和消费，将早期工作扩展到了有饮酒史的小鼠。我们假设，间歇性获得酒精和间歇性社交应激是累加的，共享引发过度饮酒的共同敏感化神经机制。
