Self-administration of inhaled delta-9-tetrahydrocannabinol and synthetic cannabinoids in non-human primates.
Self-administration of inhaled delta-9-tetrahydrocannabinol and synthetic cannabinoids in non-human primates.
复制标题
DOI：
10.1037/pha0000457
复制
发表时间：
2021-04
影响因子：
2.3
通讯作者：
Foltin RW
中科院分区：
文献类型：
--
作者：
Cooper ZD;Evans SM;Foltin RW
大麻和合成大麻素被滥用，尽管可能对健康造成不利后果。目前的研究调查了δ-9-四氢大麻酚（THC），大麻的主要精神活性成分和合成大麻素产品（JWH-018，JWH-073和HU-210）中检测到的三种合成大麻素在非人类灵长类动物（NHP）中的生态相关给药模式（吸入）的强化作用。训练雄性和雌性（各N = 4）恒河猴通过金属杆吸入热空气以接受糖果喷雾器，然后将酒精气雾剂媒介物与糖果配对。使用固定比例5强化方案建立THC（2.0-16.0 ug/kg/吸入）、JWH-018（0.2-1.6 ug/kg/吸入）、JWH-073（2.0-8.0 ug/kg/吸入）和HU-210（1.0-8.0 ug/kg/吸入）的吸入气雾剂的剂量依赖性响应，并与媒介物（酒精）自身给药进行比较。还确定了吸入海洛因（25.0-100.0 ug/kg/吸入）（一种已知的NHP中毒剂）的剂量依赖性反应。对于测试的许多药物剂量，响应接近媒介物水平，但至少一半的猴子对高于媒介物的每种大麻素和海洛因的≥一个剂量有响应，THC除外。除了THC和JWH-018（男性）外，大麻素和海洛因的药物递送（以载体百分比计算）遵循典型的倒U形剂量反应曲线。按性别分组的数据表明，男性因THC获得的车辆许可证的峰值百分比大于女性，而女性因JWH-018、HU-210和海洛因获得的车辆许可证的峰值百分比大于男性。这些发现表明，当NHP通过雾化吸入自我给药时，CB 1受体激动剂的增强作用最小。
Cannabis and synthetic cannabinoids are abused in spite of possible adverse health consequences. The current study investigated the reinforcing effects of an ecologically relevant mode of administration (inhalation) of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, and three synthetic cannabinoids detected in synthetic cannabinoid products (JWH-018, JWH-073, and HU-210) in non-human primates (NHPs). Male and female (N = 4 each) rhesus macaques were trained to inhale warm air via a metal stem to receive a candy reinforcer, an alcohol aerosol vehicle was then paired with the candy. Dose-dependent responding for inhaled aerosols of THC (2.0–16.0 ug/kg/inhalation), JWH-018 (0.2–1.6 ug/kg/inhalation), JWH-073 (2.0–8.0 ug/kg/inhalation), and HU-210 (1.0–8.0 ug/kg/inhalation) was established using a fixed-ratio 5 schedule of reinforcement and compared to vehicle (alcohol) self-administration. Dose-dependent responding for inhaled heroin (25.0–100.0 ug/kg/inhalation), a known reinforcer in NHPs, was also established. Responding approximated vehicle levels for many drug doses tested, but at least half of the monkeys responded for ≥ one dose of each cannabinoid and heroin above vehicle, with the exception of THC. Drug deliveries calculated as percent vehicle followed a prototypical inverted-U shaped dose-response curve for cannabinoids and heroin except for THC and JWH-018 (in males). Grouped data according to sex demonstrated that peak percent of vehicle reinforcers earned for THC was greater in males than females, whereas peak percent of vehicle reinforcers earned for JWH-018, HU-210, and heroin were greater in females than males. These findings indicate minimal reinforcing effects of CB1 receptor agonists when self-administered by NHPs via aerosol inhalation.
登录
查看更多内容
影响因子：
4.2
作者：
FOLTIN, RW;FISCHMAN, MW;PEARLSON, GD
通讯作者：
PEARLSON, GD
影响因子：
3.6
作者：
Hempel, Briana J.;Wakeford, Alison G. P.;Riley, Anthony L.
通讯作者：
Riley, Anthony L.
影响因子：
5
作者：
Atwood, Brady K.;Lee, Donghoon;Mackie, Ken
通讯作者：
Mackie, Ken
影响因子：
4.2
作者：
Cooper, Ziva D.;Haney, Margaret
通讯作者：
Haney, Margaret
影响因子：
3.6
作者：
Evans, SM;Nasser, J;Foltin, RW
通讯作者：
Foltin, RW