Department of Psychology, University of Guelph, Guelph, Ontario, Canada.
Pharmacol Biochem Behav. 2010 Oct;96(4):496-500. doi: 10.1016/j.pbb.2010.07.010. Epub 2010 Jul 17.
The potential of the fatty acid amide hydrolase (FAAH) inhibitor, URB597, to modify drug prime-induced reinstatement of morphine-induced conditioned floor preference or naloxone-precipitated morphine withdrawal-induced conditioned floor avoidance was evaluated. In Experiment 1, morphine-induced conditioned floor preference was established across 4 conditioning trials. Following extinction training (4 trials), rats were pretreated with URB597 or vehicle prior to a morphine prime or a saline prime. Morphine reinstated the previously extinguished floor preference, but URB597 did not modify the strength of the reinstated preference. In Experiment 2, naloxone-precipitated morphine withdrawal-induced conditioned floor avoidance was established across 2 conditioning trials. Following extinction training (14 trials), rats were pretreated with URB597 or vehicle prior to a saline prime or a morphine withdrawal prime. The morphine withdrawal prime reinstated the previously extinguished floor avoidance, but URB597 did not modify the strength of reinstated avoidance. These results suggest that under the conditions in which URB597 promotes extinction (e.g., Manwell et al. (2009)) it does not interfere with drug-induced reinstatement of either conditioned floor preference or avoidance. That is, although activation of the endocannabinoid (eCB) system promotes extinction of aversive learning, it may not prevent reinstatement of that aversion by re-exposure to the aversive treatment.
评估了脂肪酸酰胺水解酶（FAAH）抑制剂 URB597 修饰药物引发的吗啡诱导的条件性地板偏好复燃或纳洛酮引发的吗啡戒断诱导的条件性地板回避的潜力。在实验 1 中，通过 4 个条件性试验建立了吗啡诱导的条件性地板偏好。在消退训练（4 次试验）后，大鼠在接受吗啡引发或生理盐水引发之前，预先接受 URB597 或载体处理。吗啡复燃了先前消退的地板偏好，但 URB597 并没有改变复燃偏好的强度。在实验 2 中，通过 2 个条件性试验建立了纳洛酮引发的吗啡戒断诱导的条件性地板回避。在消退训练（14 次试验）后，大鼠在接受生理盐水引发或吗啡戒断引发之前，预先接受 URB597 或载体处理。吗啡戒断引发复燃了先前消退的地板回避，但 URB597 并没有改变复燃回避的强度。这些结果表明，在 URB597 促进消退的条件下（例如，Manwell 等人，2009 年），它不会干扰药物引发的条件性地板偏好或回避的复燃。也就是说，尽管内源性大麻素（eCB）系统的激活促进了厌恶学习的消退，但它可能无法防止重新暴露于厌恶治疗时对该厌恶的复燃。
