Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Pharmacol Biochem Behav. 2021 Mar;202:173116. doi: 10.1016/j.pbb.2021.173116. Epub 2021 Jan 23.
Advances in drug vapor exposure systems have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; and 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Sprague Dawley and Wistar rats (N = 22, 5-6/sex per group) received THC via passive vapor exposure (200 mg/mL; 5 conditions) and IP injection (1-20 mg/kg) in a within subject design. The effects of vaped and injected THC on appetite was determined using progressive ratio responding for food pellets. THC effects on nociception, measured using the tail withdrawal assay, and body temperature were also assessed during a 5-h test period for evaluation of time course of effects. Plasma THC concentrations were assessed after THC vapor and 10 mg/kg IP THC. THC vapor produced exposure-related increases and decreases in motivation to obtain food under the progressive ratio schedule. IP THC (3-20 mg/kg) reduced breakpoints. Vaped and injected THC produced exposure and dose-dependent antinociception and hypothermia. Sex and strain differences in THC effects were also observed. Plasma THC concentrations were higher after 10 mg/kg IP THC (152 ng/mL) compared to the highest vapor exposure condition tested (38 ng/mL), but magnitude of behavioral effects were comparable. THC vapor exposure produced reliable, dose orderly effects on food-maintained behavior, nociception, and body temperature that are comparable to effects of IP THC, although there were differences in the time course of behavioral outcomes.
药物蒸气暴露系统的进步使人们能够评估 Δ-9-四氢大麻酚（THC）蒸气对实验室动物的影响。本研究的目的是：1）确定足以在一系列对 THC 敏感的任务中产生行为剂量-效应曲线的 THC 蒸气暴露参数范围；2）研究 THC 蒸气暴露和 THC 注射（腹腔内，IP）对两种近交系大鼠这些行为的影响的性别差异。雄性和雌性 Sprague Dawley 和 Wistar 大鼠（N = 22，每组 5-6/性别）通过被动蒸气暴露（200 mg/mL；5 种条件）和 IP 注射（1-20 mg/kg）在一个个体内设计中接受 THC。使用食物颗粒的递增比率反应确定蒸气和注射 THC 对食欲的影响。使用尾巴撤回试验评估 THC 对痛觉的影响，并在 5 小时的测试期间评估体温，以评估作用时间过程。在 THC 蒸气和 10 mg/kg IP THC 后评估血浆 THC 浓度。THC 蒸气产生了与暴露相关的动机增加和减少，以获得递增比率计划下的食物。IP THC（3-20 mg/kg）降低了断点。蒸气和注射 THC 产生了暴露和剂量依赖性的镇痛和体温降低。还观察到 THC 效应的性别和品系差异。与测试的最高蒸气暴露条件（38 ng/mL）相比，10 mg/kg IP THC（152 ng/mL）后血浆 THC 浓度更高，但行为效应的幅度相当。尽管行为结果的时间过程存在差异，但 THC 蒸气暴露对食物维持行为、痛觉和体温产生了可靠的、剂量有序的影响，与 IP THC 的影响相当。
