Addiction Neuroscience Graduate Program, Department of Psychology, Indiana University-Purdue University Indianapolis, 402 North Blackford Street, Indianapolis, IN 46202, United States of America.
Addiction Neuroscience Graduate Program, Department of Psychology, Indiana University-Purdue University Indianapolis, 402 North Blackford Street, Indianapolis, IN 46202, United States of America.
Pharmacol Biochem Behav. 2019 Dec;187:172816. doi: 10.1016/j.pbb.2019.172816. Epub 2019 Oct 22.
Increased subjective discounting of delayed rewards is associated with substance abuse, and individuals tend to discount their drug of choice at a greater rate compared to monetary rewards. While there is evidence indicating that increased delay discounting (DD) is a risk factor for substance abuse, some results suggest that exposure to drugs of abuse also increases DD, but effects are mixed. The current study examined whether ethanol pre-exposure increases DD and if an ethanol reinforcer would be discounted at a greater rate than sucrose. Alcohol preferring (P) rats were pre-exposed to either ethanol or sucrose using an intermittent access protocol (IAP) for 8 weeks. Then animals completed an operant fixed choice procedure where each pre-exposure group was split into either an ethanol or sucrose reinforcer group. Afterwards, animals completed an adjusting delay DD task using the same groups as the fixed choice task. Animals that received access to ethanol in the IAP showed increased delayed reward preference in a delay and session dependent manner. Specifically, ethanol pre-exposed animals took more sessions to decrease their preference for the delayed reward at longer delays. In the adjusting delay task, no differences in mean adjusting delays were seen, but ethanol pre-exposure impaired animals' ability to reach stability criteria. The observed results are not consistent with ethanol pre-exposure causing a change in DD. Rather they indicate ethanol pre-exposure impaired animals' ability to reallocate their behavior in response to a change in reinforcer contingencies. The current findings extend prior results showing alcohol naïve P rats exhibit both increased DD and decreased response inhibition (Beckwith and Czachowski 2014, 2016) by demonstrating that after alcohol exposure they exhibit a form of behavioral inflexibility. Hence, a "two-hit" genetic vulnerability/environmental acceleration of addictive behavior is supported.
延迟奖励的主观折扣增加与物质滥用有关,与金钱奖励相比,个体往往会更大程度地折扣他们选择的药物。虽然有证据表明,延迟折扣(DD)增加是物质滥用的一个风险因素,但一些结果表明,滥用药物的暴露也会增加 DD,但效果不一。本研究考察了乙醇预暴露是否会增加 DD,以及乙醇强化物是否会比蔗糖更快地被折扣。使用间歇访问协议(IAP),对酒精偏好(P)大鼠进行了 8 周的乙醇或蔗糖预暴露。然后,动物完成了一个操作性固定选择程序,其中每个预暴露组被分为乙醇或蔗糖强化物组。之后,动物使用与固定选择任务相同的组完成了一个调整延迟 DD 任务。在 IAP 中获得乙醇的动物表现出延迟奖励偏好的延迟和会话依赖性增加。具体来说,乙醇预暴露的动物需要更多的会话来减少对较长延迟的延迟奖励的偏好。在调整延迟任务中,平均调整延迟没有差异,但乙醇预暴露损害了动物达到稳定标准的能力。观察到的结果与乙醇预暴露导致 DD 变化不一致。相反,它们表明,乙醇预暴露损害了动物根据强化物关联的变化重新分配行为的能力。当前的发现通过证明酒精暴露后,它们表现出一种行为灵活性,扩展了先前的结果,这些结果表明,酒精-naive P 大鼠表现出增加的 DD 和减少的反应抑制(Beckwith 和 Czachowski,2014 年,2016 年)。因此,支持遗传易感性/环境加速成瘾行为的“双重打击”。