Manning R J
Pharmacol Biochem Behav. 1976 Jan;4(1):17-21. doi: 10.1016/0091-3057(76)90169-6.
Delta-9-Tetrahydrocannabinol (THC) was administered to albino rats with extensive experience in free-operant (Sidman) lever-press shock avoidance. Dosing (30 mg/kg intragastrically) continued once daily, 3 hr before testing, for 1 to 6 weeks. Significant changes were noted in the response rates of several animals, but both the magnitude and direction of these were highly variable. However, shock rates were reliably elevated by THC, but complete tolerance was observed within 6 sessions. In several rats this was followed by sessions with significantly lower shock rates than the predrug baseline. These rats continued to perform at this level of proficiency until THC was discontinued, at which point the baseline was reacquired. These data emphasize that an important determinant of tolerance to a drug effect is the consequence of the effect for the organism.
将Δ-9-四氢大麻酚(THC)给予在自由操作(西德曼)杠杆按压避免电击实验中有丰富经验的白化大鼠。给药(30毫克/千克,胃内给药)每天一次,在测试前3小时进行,持续1至6周。观察到几只动物的反应率有显著变化,但这些变化的幅度和方向高度可变。然而,THC确实可靠地提高了电击率,但在6次实验内就观察到了完全耐受性。在几只大鼠中,随后出现了电击率明显低于给药前基线的实验阶段。这些大鼠在THC停药之前一直保持这种熟练程度,停药后又恢复到基线水平。这些数据强调,对药物效应耐受性的一个重要决定因素是该效应对机体的影响结果。