Psychology Department, Washington State University, PO Box 644820, Pullman, WA, 99164-4820, USA.
Psychopharmacology (Berl). 2022 May;239(5):1563-1578. doi: 10.1007/s00213-022-06094-9. Epub 2022 Mar 10.
Adolescent cannabinoid exposure has been shown to alter cognitive, reward-related, and motor behaviors as well as mesocorticolimbic dopamine (DA) function in adult animals. Pain is also influenced by mesocorticolimbic DA function, but it is not known whether pain or cannabinoid analgesia in adults is altered by early exposure to cannabinoids.
To determine whether adolescent Δ-tetrahydrocannabinol (THC) exposure alters pain-related behaviors before and after induction of persistent inflammatory pain, and whether it influences antinociceptive of THC, in adult rats, and to compare the impact of adolescent THC exposure on pain to its effects on known DA-dependent behaviors such as exploration and consumption of a sweet solution.
Vehicle or THC (2.5 to 10 mg/kg s.c.) was administered daily to male and female rats on post-natal day (PND) 30-43. In adulthood (PND 80-88), sensitivity to mechanical and thermal stimuli before and after intraplantar injection of complete Freund's adjuvant (CFA) was determined. Antinociceptive, exploratory, and consummatory effects of 2.0 mg/kg THC were then examined.
Adolescent THC exposure did not significantly alter adult sensitivity to non-noxious or noxious stimuli either before or after CFA injection, nor did it alter the antinociceptive effect of THC. In contrast, adolescent THC exposure altered adult exploratory and consummatory behaviors in a sex-dependent manner: when tested as adults, adolescent THC-treated males showed less hedonic drinking than adolescent vehicle-treated males, and females but not males that had been THC-exposed as adolescents showed reduced sensitivity to THC-induced suppression of activity and THC-induced hedonic drinking as adults.
Adolescent THC exposure that altered both exploratory and consummatory behaviors in adults did not alter pain-related behaviors either before or after induction of inflammatory pain, suggesting that cannabinoid exposure during adolescence is not likely to substantially alter pain or cannabinoid analgesia in adulthood.
青春期大麻素暴露已被证明会改变成年动物的认知、奖励相关和运动行为以及中皮质边缘多巴胺（DA）功能。疼痛也受中皮质边缘 DA 功能的影响，但尚不清楚成年人的疼痛或大麻素镇痛是否会因早期接触大麻素而改变。
确定青春期 Δ-四氢大麻酚（THC）暴露是否会改变慢性炎症性疼痛诱导前后与疼痛相关的行为，以及它是否会影响成年大鼠中 THC 的镇痛作用，并比较青春期 THC 暴露对疼痛的影响与它对已知的依赖多巴胺的行为（如探索和食用甜溶液）的影响。
在出生后第 30-43 天（PND），给雄性和雌性大鼠每天皮下注射载体或 THC（2.5 至 10 mg/kg）。在成年期（PND 80-88），通过足底注射完全弗氏佐剂（CFA）前后测定对机械和热刺激的敏感性。然后检查 2.0 mg/kg THC 的镇痛、探索和消耗作用。
青春期 THC 暴露既没有显著改变成年后对非伤害性或伤害性刺激的敏感性，也没有改变 THC 的镇痛作用。相比之下，青春期 THC 暴露以性别依赖的方式改变了成年后的探索和消耗行为：作为成年人进行测试时，与青春期接受载体治疗的雄性相比，青春期接受 THC 治疗的雄性的快感性饮酒量减少，而青春期接受 THC 暴露的雌性，但不是雄性，表现出对 THC 诱导的活动抑制和快感性饮酒的敏感性降低。
改变成年后探索和消耗行为的青春期 THC 暴露既没有改变炎症性疼痛诱导前后与疼痛相关的行为，这表明青春期接触大麻素不太可能在成年期显著改变疼痛或大麻素镇痛。
