Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.
J Neurosci Methods. 2021 Apr 15;354:109110. doi: 10.1016/j.jneumeth.2021.109110. Epub 2021 Mar 8.
Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders.
The aims were to back-translate an intravenous drug-vs-food choice procedure primarily utilized in monkeys to male and female rats and to develop a surgical method for sustained intravenous catheter patency suitable for long-term drug-choice studies.
The surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days (range: 25-365 days). Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions (range: 16-44 sessions). Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables (e.g., response requirement or food reinforcer magnitude) and pharmacological variables (e.g., extended access drug self-administration or continuous buprenorphine treatment via osmotic pump) significantly shifted opioid-vs-food choice consistent with previous monkey studies.
Duration of intravenous catheter patency in rats was suitable for long-term, within-subject drug choice studies. Effects of environmental and pharmacological manipulations in rats confirmed and extended previous results from monkeys.
The concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.
临床前药物自我给药程序常用于研究物质使用障碍的表达、机制和治疗。
目的是将主要用于猴子的静脉药物与食物选择程序反向翻译为雄性和雌性大鼠，并开发一种适合长期药物选择研究的持续静脉导管通畅性的手术方法。
手术方案使雄性和雌性大鼠的中位静脉颈内导管通畅时间为 126 天（范围：25-365 天）。使用阿片类药物（芬太尼和海洛因）、精神兴奋剂（可卡因、甲基苯丙胺和苯丙胺）和阿片类药物/精神兴奋剂混合物（芬太尼+甲基苯丙胺）建立了药物与食物的选择。从导管植入到所有药物稳定选择行为的平均时间为 27 个疗程（范围：16-44 个疗程）。可卡因和芬太尼的选择行为比其他药物稳定得更快。环境变量（例如，反应要求或食物强化剂的大小）和药理学变量（例如，延长的药物自我给药或通过渗透泵持续给予丁丙诺啡治疗）的操作都显著改变了阿片类药物与食物的选择，与之前的猴子研究一致。
大鼠静脉导管通畅时间适合长期、个体内药物选择研究。大鼠的环境和药理学操作的影响证实并扩展了猴子的先前结果。
使用本药物与食物选择程序，大鼠和猴子的行为结果的一致性支持其用于提高我们对物质使用障碍表达和机制的基本理解，以开发更有效的治疗方法。
