Amirali Alishan S, Hecker Jacquelin C, Figueroa Hector M, Effinger Devin P, Montoro Rodrigo A, Jedema Hank P, Vogt Caleb D, Newman Amy Hauck, Schindler Charles W, Bradberry Charles W
Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural research Program, Baltimore, MD, USA.
Department of Pharmacology, University of North Carolina Chapel Hill, Chapel Hill, NC.
Addict Neurosci. 2023 Mar;5. doi: 10.1016/j.addicn.2023.100065. Epub 2023 Jan 18.
We recently reported an economic choice task in which squirrel monkeys chose between differing amounts of remifentanil, a fast-acting opioid, or a food reward to develop a preclinical screen for evaluating potential pharmacotherapies for opioid dependence. Herein, two known opioid addiction treatments are evaluated using this task, as well as a potential new agent, cariprazine, a dopamine D2/D3 receptor partial agonist currently used to treat bipolar disorder and schizophrenia. Preclinical rodent studies suggest this class of compounds may reduce opiate self-administration. Squirrel monkeys were pretreated daily with clinically relevant doses of each compound during the five days of treatment evaluation using the economic choice task. Shifts in drug preference were measured as changes in subjects' indifference values, where the probability of drug and milk choice are equivalent. Buprenorphine produced a significant shift in indifference value between baseline and treatment weeks, indicating a decrease in drug preference. Subjects treated with methadone and cariprazine did not show any significant shift in drug preference. Differences between the buprenorphine and methadone results likely reflect a lack of opioid dependence in the subjects. The cariprazine results suggest that it does not alter opioid reward in non-dependent primates over a five day period.
我们最近报告了一项经济选择任务,在该任务中,松鼠猴在不同剂量的瑞芬太尼(一种速效阿片类药物)或食物奖励之间进行选择,以开发一种临床前筛选方法,用于评估阿片类药物依赖的潜在药物治疗方法。在此,使用该任务评估了两种已知的阿片类药物成瘾治疗方法,以及一种潜在的新药卡立普多,它是一种多巴胺D2/D3受体部分激动剂,目前用于治疗双相情感障碍和精神分裂症。临床前啮齿动物研究表明,这类化合物可能会减少阿片类药物的自我给药。在使用经济选择任务进行治疗评估的五天内,每天用临床相关剂量的每种化合物对松鼠猴进行预处理。药物偏好的变化通过受试者无差异值的变化来衡量,即药物和牛奶选择的概率相等时的变化。丁丙诺啡在基线期和治疗期之间的无差异值有显著变化,表明药物偏好降低。接受美沙酮和卡立普多治疗的受试者在药物偏好上没有显示出任何显著变化。丁丙诺啡和美沙酮结果之间的差异可能反映了受试者缺乏阿片类药物依赖。卡立普多的结果表明,在五天的时间里,它不会改变非依赖灵长类动物的阿片类药物奖励。