Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Pharmacol Biochem Behav. 2020 Oct;197:173002. doi: 10.1016/j.pbb.2020.173002. Epub 2020 Jul 23.
The rate of cannabinoid intake by those with alcohol use disorder (AUD) exceeds that of the general public. The high prevalence of co-abuse of alcohol and cannabis has been postulated to be predicated upon both a common predisposing genetic factor and the interaction of the drugs within the organism. The current experiments examined the effects of cannabinoids in an animal model of AUD.
The present study assessed the reinforcing properties of a cannabinoid receptor 1 (CB1) agonist self-administered directly into the nucleus accumbens shell (AcbSh) in female Wistar and alcohol-preferring (P) rats.
Following guide cannulae surgery aimed at AcbSh, subjects were placed in an operant box equipped with an 'active lever' (fixed ratio 1; FR1) that caused the delivery of the infusate and an 'inactive lever' that did not. Subjects were arbitrarily assigned to one of seven groups that self-administered either artificial cerebrospinal fluid (aCSF), or 3.125, 6.25, 12.5, or 25 pmol/100 nl of O-1057, a water-soluble CB1 agonist, dissolved in aCSF. The first four sessions of acquisition are followed by aCSF only infusates in sessions 5 and 6 during extinction, and finally the acquisition dose of infusate during session 7 as reinstatement.
The CB1 agonist was self-administered directly into the AcbSh. P rats self-administered the CB1 agonist at lower concentrations and at higher rates compared to Wistar rats.
Overall, the data indicate selective breeding for high alcohol preference has produced rats divergent in response to cannabinoids within the brain reward pathway. The data support the hypothesis that there can be common genetic factors influencing drug addiction.
患有酒精使用障碍（AUD）的人摄入大麻素的比率超过了普通公众。酒精和大麻共同滥用的高患病率被认为是基于共同的遗传易感性因素和药物在体内的相互作用。目前的实验研究了大麻素在 AUD 动物模型中的作用。
本研究评估了大麻素受体 1（CB1）激动剂直接注入伏隔核壳（AcbSh）在雌性 Wistar 和酒精偏好（P）大鼠中的强化作用。
在 AcbSh 进行导向套管手术后，将受试动物置于配备“主动杆”（固定比 1；FR1）的操作箱中，该主动杆会引发输注液的输送，而“被动杆”则不会。受试动物被任意分配到七个组中的一个，这些组分别自我注射人工脑脊液（aCSF），或溶于 aCSF 的 3.125、6.25、12.5 或 25 pmol/100 nl 的 O-1057，一种水溶性 CB1 激动剂。在获得期的前四个阶段之后，在消退阶段的第五和第六个阶段只注射 aCSF 输注液，最后在第七个阶段恢复获得期的输注液剂量。
CB1 激动剂直接注入 AcbSh。与 Wistar 大鼠相比，P 大鼠以较低的浓度和较高的速度自我注射 CB1 激动剂。
总体而言，数据表明，对高酒精偏好的选择性繁殖产生了对大脑奖励途径中的大麻素反应不同的大鼠。该数据支持存在影响药物成瘾的共同遗传因素的假设。
