Marchant Nathan J, Campbell Erin J, Kaganovsky Konstantin
Anatomy & Neurosciences Department, VUmc, Amsterdam, The Netherlands; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Dec 20;87(Pt A):68-77. doi: 10.1016/j.pnpbp.2017.07.020. Epub 2017 Jul 25.
Individual variations in animal behaviour can be used to describe relationships between different constructs, as well as the underlying neurobiological mechanisms responsible for such variation. In humans, variation in the expression of certain traits contributes to the onset of psychopathologies, such as drug addiction. Addiction is characterised by persistent drug use despite negative consequences, but it occurs in only a sub-population of drug users. Compulsive drug use is modelled in laboratory animals by punishing a drug-reinforced operant response. It has been reported that there is individual variability in the response to punishment, and in this report we aim to further define the conditions under which this variation can be observed. We have previously used footshock punishment to suppress alcohol seeking in an animal model of context-induced relapse to alcohol seeking after punishment-imposed abstinence. Here we present a re-examination of the training and punishment data from a large cohort of rats (n=499) collected over several years. We found evidence for a bimodal distribution in the response to punishment in alcohol preferring P rats. We only observed this population split when rats received constant shock intensity for three sessions, but not when increasing shock intensity was used. This observation provides evidence for the existence of two distinct groups of rats, defined by their response to punishment, in an otherwise homogeneous population. The implications of this observation are discussed in reference to prior observations using punishment of other addictive drugs (cocaine and methamphetamine), the potential causes of this phenomenon, and with broader implications for the cause of alcohol and drug addiction in humans.
动物行为的个体差异可用于描述不同结构之间的关系，以及导致这种差异的潜在神经生物学机制。在人类中，某些特质表达的差异会导致精神病理学的发生，如药物成瘾。成瘾的特征是尽管有负面后果仍持续使用药物，但它仅发生在一部分吸毒人群中。在实验室动物中，通过惩罚药物强化的操作性反应来模拟强迫性药物使用。据报道，对惩罚的反应存在个体差异，在本报告中，我们旨在进一步确定观察到这种差异的条件。我们之前曾使用足部电击惩罚来抑制在惩罚性戒断后情境诱导的酒精寻求复发的动物模型中的酒精寻求行为。在这里，我们对多年来收集的大量大鼠（n = 499）的训练和惩罚数据进行了重新审视。我们发现，在偏好酒精的P大鼠对惩罚的反应中存在双峰分布的证据。只有当大鼠在三个实验环节中接受恒定的电击强度时，我们才观察到这种群体划分，而当使用逐渐增加的电击强度时则没有观察到。这一观察结果为在原本同质的群体中存在由对惩罚的反应定义的两个不同大鼠群体提供了证据。我们参考之前使用其他成瘾药物（可卡因和甲基苯丙胺）惩罚的观察结果、这种现象的潜在原因以及对人类酒精和药物成瘾原因的更广泛影响，讨论了这一观察结果的意义。
