Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Addict Biol. 2024 Oct;29(10):e13442. doi: 10.1111/adb.13442.
Increased allocation of behaviour to substance abuse at the expense of personal and social rewards is a hallmark of addiction that is reflected in several of DSM-5 criteria for diagnosis of substance use disorder. Previous studies focused on refining the self-administration (SA) model to better emulate an addictive state in laboratory animals. Here, we employed concurrent SA of sucrose pellets and morphine as two competing natural and drug rewards, respectively, to validate the feasibility of capturing pathological behavioural allocation in rats. A custom-made three-lever operant chamber was used. With one active and one inactive lever presented, rats were trained to self-administer morphine (0.5 mg/kg/infusion; 2 h/day) under a fixed-ratio 1 (FR-1) schedule until a stable response was achieved. Next, they were trained to self-administer morphine in the presence of a third lever dispensing sucrose pellets (20 mg) under FR-1. Concurrent morphine-sucrose SA sessions (2 h/day) were continued until stable morphine taking behaviour was re-established. In another experiment, rats first established stable sucrose pellet SA (2 h/day, FR-1) and then were trained to take morphine (0.5 mg/kg/infusion; 2 h/day). Subsequently, all rats underwent extinction training, in which morphine was replaced with saline while sucrose pellets were still available upon lever pressing, followed by cue-induced reinstatement of morphine seeking behaviour. Results showed that rats retained morphine SA when sucrose pellets were also available, but they showed binge-like sucrose intake when morphine was removed during the extinction sessions. However, morphine SA did not develop in rats that had previously established sucrose pellet SA. In conclusion, morphine SA developed even in the presence of a potent competing nondrug reward in rats. Adding an effort-based contingent delivery of a natural reward to the standard SA model, this protocol may provide an improved model of drug addiction in laboratory animals.
在成瘾中，行为分配给物质滥用而不是个人和社会奖励的增加是一个标志，这反映在 DSM-5 中用于诊断物质使用障碍的几个标准中。以前的研究集中于改进自我给药 (SA) 模型，以更好地模拟实验室动物中的成瘾状态。在这里，我们分别使用蔗糖丸和吗啡的同时 SA 作为两种竞争的天然和药物奖励，以验证在大鼠中捕获病理性行为分配的可行性。使用定制的三杠杆操作室。当呈现一个活动杠杆和一个非活动杠杆时，训练大鼠根据固定比率 1 (FR-1) 方案自我给药吗啡 (0.5 mg/kg/输注；每天 2 小时)，直到获得稳定的反应。接下来，在第三个分配蔗糖丸 (20 mg) 的杠杆存在下，训练它们自我给药吗啡。继续进行同时的吗啡-蔗糖 SA 会议 (每天 2 小时)，直到重新建立稳定的吗啡摄取行为。在另一个实验中，大鼠首先建立稳定的蔗糖丸 SA (每天 2 小时，FR-1)，然后接受吗啡 (0.5 mg/kg/输注；每天 2 小时) 的训练。随后，所有大鼠都接受了消退训练，其中吗啡被生理盐水替代，而当按压杠杆时仍可获得蔗糖丸，随后是线索诱导的吗啡寻求行为的复燃。结果表明，当蔗糖丸也可用时，大鼠保留了吗啡 SA，但在消退期间吗啡被去除时，它们表现出 binge-like 蔗糖摄入。然而，以前建立了蔗糖丸 SA 的大鼠并没有发展出吗啡 SA。总之，即使在存在强效竞争的非药物奖励的情况下，吗啡 SA 也在大鼠中发展。在标准 SA 模型中添加基于努力的自然奖励的条件性交付，该方案可能为实验室动物中的药物成瘾提供一种改进的模型。
