School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
Behav Brain Res. 2021 Mar 5;401:113090. doi: 10.1016/j.bbr.2020.113090. Epub 2020 Dec 28.
Substance use disorders are a debilitating neuropsychiatric condition, however it remains unclear why some individuals are at greater risk of substance use disorders than others and what genetic factors determine such individual differences. Impulsivity appears a promising candidate endophenotype to bridge the gap between genetic risk and addiction. Brain-derived neurotrophic factor (BDNF), and in particular the BDNF polymorphism, has been suggested to be involved in both impulsivity and substance use disorders, however results so far have been inconsistent. To investigate the role of BDNF, and more specifically the BDNF polymorphism, in both impulsivity and operant alcohol self-administration using the same animal model. Separate cohorts of humanized Val66Met transgenic mice were assessed for either trait impulsivity in the 5-choice serial reaction time (5-CSRT) touchscreen task, or propensity towards obtaining ethanol in an operant paradigm. It was found that female hBDNF mice exhibited both greater impulsivity compared to hBDNF mice of the same sex as shown by a higher number of premature responses at one of three increased inter-trial intervals tested in the 5-CSRT task, and a greater propensity toward stable ethanol self-administration relative to male mice of the same genotype in the operant paradigm. By contrast, male mice showed no difference between genotypes in impulsivity or stable ethanol self-administration. The hBDNF genotype appears to sex-specifically alter aspects of both impulsive behaviour and addiction propensity. These results suggest that impulse behaviour may be a possible predictor of addiction risk.
物质使用障碍是一种使人衰弱的神经精神疾病，但仍不清楚为什么有些人比其他人更容易患物质使用障碍，以及哪些遗传因素决定了这种个体差异。冲动性似乎是一种有前途的候选内表型，可以弥合遗传风险和成瘾之间的差距。脑源性神经营养因子（BDNF），特别是 BDNF 多态性，被认为与冲动性和物质使用障碍都有关，但迄今为止的结果并不一致。为了研究 BDNF，特别是 BDNF 多态性，在使用相同动物模型的冲动性和操作性酒精自我给药中的作用。分别评估了人类化 Val66Met 转基因小鼠的两种特征冲动性，即在 5 选择连续反应时间（5-CSRT）触摸屏任务中的冲动性，或在操作性范式中获得乙醇的倾向。结果发现，与具有相同性别的 hBDNF 小鼠相比，雌性 hBDNF 小鼠在 5-CSRT 任务中三个增加的试验间间隔中的一个中表现出更高的过早反应次数，从而显示出更高的冲动性，并且在操作性范式中，与具有相同基因型的雄性小鼠相比，具有更高的稳定乙醇自我给药倾向。相比之下，雄性小鼠在冲动性或稳定乙醇自我给药方面没有表现出基因型差异。hBDNF 基因型似乎特异性地改变了冲动行为和成瘾倾向的各个方面。这些结果表明，冲动行为可能是成瘾风险的一个可能预测因素。
