Selective breeding for high alcohol preference is associated with increased sensitivity to cannabinoid reward within the nucleus accumbens shell.,Pharmacology Biochemistry and Behavior

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Selective breeding for high alcohol preference is associated with increased sensitivity to cannabinoid reward within the nucleus accumbens shell.
Pharmacology Biochemistry and Behavior ( IF 3.6 ) Pub Date : 2020-07-23 , DOI: 10.1016/j.pbb.2020.173002
Sheketha R Hauser ₁ , Simon N Katner ₁ , Robert A Waeiss ₁ , William A Truitt ₂ , Richard L Bell ₁ , William J McBride ₁ , Zachary A Rodd ₁

Affiliation

Rationale

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

高酒精偏好的选择性育种与伏隔核壳内对大麻素奖励的敏感性增加有关。

基本原理

酒精使用障碍（AUD）患者的大麻素摄入率超过了普通大众。酒精和大麻共同滥用的高发率被假定是基于共同的遗传易感因素和生物体内药物的相互作用。当前的实验检查了大麻素在 AUD 动物模型中的作用。

目标

本研究评估了大麻素受体 1 (CB1) 激动剂直接自我给药到雌性 Wistar 和嗜酒 (P) 大鼠伏核壳 (AcbSh) 的增强特性。

方法

在针对 AcbSh 的引导套管手术之后，受试者被放置在一个配备有“主动杠杆”（固定比率 1；FR1）的操作箱中，该杠杆导致输液的输送，而“非活动杠杆”则不会。受试者被任意分配到七个组中的一个，这些组自我管理人工脑脊液 (aCSF)，或 3.125、6.25、12.5 或 25 pmol/100 nl 的 O-1057，一种水溶性 CB1 激动剂，溶解在 aCSF 中。前四次收购之后是 aCSF 仅在第 5 次和第 6 次消退期间注入，最后在第 7 次会议期间注入剂量作为恢复。