Program in Behavioral Neuroscience, Department of Psychology, The State University of New York University at Buffalo, 214 Park Hall, Buffalo, NY, 14260, USA.
Sci Rep. 2021 Feb 8;11(1):3321. doi: 10.1038/s41598-021-81955-5.
Habitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, and 20 mg/kg), while shifting the dose-response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.
习惯性使用含尼古丁产品会增加滥用处方类阿片的倾向，而且在目前参与阿片类药物治疗计划的个体中，其流行率大大增加。尼古丁增强了啮齿动物对许多类药物的自我给药，尽管缺乏对阿片类药物的直接影响的证据。我们试图测量尼古丁预处理对阿片类药物自我给药和情境条件反射范式中强化效力的影响。首先，我们测量了全身尼古丁预处理对两种阿片类药物自我给药的影响。此外，我们还测量了全身尼古丁预处理对条件性味觉回避和位置偏好范式中吗啡相关情境记忆形成的影响程度。鉴于脑岛在维持物质滥用中的作用，在尼古丁成瘾中的重要性，以及发现脑岛失活会损害情境药物条件反射，我们研究了直接向脑岛给予尼古丁是否可以重现全身尼古丁的作用。我们证明，全身尼古丁预处理显著增强了阿片类药物的自我给药，并改变了情境条件反射。此外，内侧脑岛中的尼古丁也通过阻断在所有三种测试的吗啡剂量（5.0、10 和 20mg/kg）下的味觉回避，改变了吗啡的情境条件反射，同时将吗啡在位置偏好范式中的剂量反应曲线向右移动，从而类似地改变了吗啡的情境条件反射。总之，这些数据表明，尼古丁促进阿片类药物的摄入，并且部分作用于脑岛皮层，以混淆厌恶的阿片类记忆，同时增强对高剂量吗啡相关刺激的接近。
