Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice.
Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice.
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DOI：
10.1016/j.drugalcdep.2014.11.015
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发表时间：
2015-01-01
影响因子：
4.2
通讯作者：
Lichtman, Aron H.
中科院分区：
文献类型：
--
作者：
Gamage, Thomas F.;Ignatowska-Jankowsa, Bogna M.;Muldoon, Pretal P.;Cravatt, Benjamin F.;Damaj, M. Imad;Lichtman, Aron H.
关键词：
抑制内源性大麻素分解代谢酶脂肪酸酰胺水解酶（FAAH）和/或单酰甘油脂肪酶（MAGL）可减少躯体吗啡戒断症状，但其对戒断厌恶方面的影响尚不清楚。本研究调查了 Δ9-四氢大麻酚 (THC)、MAGL 抑制剂 JZL184、FAAH 抑制剂 PF-3845 或双重 FAAH/MAGL 抑制剂 SA-57 是否会减少吗啡戒断引起的条件性位置回避 (CPA) 和跳跃的获得。给小鼠植入安慰剂或 75 mg 吗啡颗粒，48 小时后注射纳洛酮或盐水，并置于调节装置中，并在 72 小时评估 CPA。还观察了受试者在纳洛酮挑战后的跳跃行为。纳洛酮 (0.056 mg/kg) 在注射吗啡颗粒的小鼠中产生强烈的 CPA，但在注射安慰剂颗粒的小鼠中则不然。吗啡预处理可预防戒断性CPA和戒断跳跃的发生，而可乐定（α2肾上腺素受体激动剂）仅阻断戒断性CPA。 THC、JZL184 和 SA-57 显着降低了调节过程中小鼠跳跃的百分比，但不影响戒断 CPA 的获得。 PF-3845 不会降低吗啡戒断 CPA 或跳跃。最后，在非依赖性小鼠中，四氢大麻酚和内源性大麻素分解代谢酶抑制剂都不会引起条件性位置偏好或厌恶。这些发现表明，抑制内源性大麻素分解代谢酶可以减少体细胞吗啡戒断症状，但不能减少 CPA 范式中推断的厌恶症状。观察到给予内源性大麻素降解抑制剂的非依赖性小鼠没有表现出位置偏好，这与内源性大麻素分解代谢酶可能成为治疗目标并降低滥用风险的想法是一致的。
Inhibition of endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and/or monoacylglycerol lipase (MAGL) reduces somatic morphine withdrawal signs, but its effects on aversive aspects of withdrawal are unknown. The present study investigated whether Δ9-tetrahydrocannabinol (THC), the MAGL inhibitor JZL184, the FAAH inhibitor PF-3845, or the dual FAAH/MAGL inhibitor SA-57 would reduce acquisition of morphine withdrawal-induced conditioned place avoidance (CPA) and jumping. Mice were implanted with placebo or 75 mg morphine pellets, 48 h later injected with naloxone or saline and placed in the conditioning apparatus, and assessed for CPA at 72 h. Subjects were also observed for jumping behavior following naloxone challenge. Naloxone (0.056 mg/kg) produced robust CPA in morphine-pelleted, but not placebo-pelleted, mice. Morphine pretreatment prevented the occurrence of withdrawal CPA and withdrawal jumping, while clonidine (an α2 adrenergic receptor agonist) only blocked withdrawal CPA. THC, JZL184, and SA-57 significantly reduced the percentage of mice that jumped during the conditioning session, but did not affect acquisition of withdrawal CPA. PF-3845 did not reduce morphine withdrawal CPA or jumping. Finally, neither THC nor the endocannabinoid catabolic enzyme inhibitors in non-dependent mice elicited a conditioned place preference or aversion. These findings suggest that inhibiting endocannabinoid catabolic enzymes reduces somatic morphine withdrawal signs, but not aversive aspects as inferred in the CPA paradigm. The observation that non-dependent mice administered inhibitors of endocannabinoid degradation did not display place preferences is consistent with the idea that that endocannabinoid catabolic enzymes might be targeted therapeutically, with reduced risk of abuse.
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影响因子：
10.6
作者：
Justinova, Zuzana;Mangieri, Regina A.;Bortolato, Marco;Chefer, Svetlana I.;Mukhin, Alexey G.;Clapper, Jason R.;King, Alvin R.;Redhi, Godfrey H.;Yasar, Sevil;Piomelli, Daniele;Goldberg, Steven R.
通讯作者：
Goldberg, Steven R.
DOI：
10.1034/j.1600-0773.2001.d01-146.x
发表时间：
2001-09-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
Dehpour, AR;Samini, M;Namiranian, K
通讯作者：
Namiranian, K
影响因子：
--
作者：
Ahn K;Johnson DS;Mileni M;Beidler D;Long JZ;McKinney MK;Weerapana E;Sadagopan N;Liimatta M;Smith SE;Lazerwith S;Stiff C;Kamtekar S;Bhattacharya K;Zhang Y;Swaney S;Van Becelaere K;Stevens RC;Cravatt BF
通讯作者：
Cravatt BF
影响因子：
1.6
作者：
Broseta, I;Rodriguez-Arias, M;Mi単arro, J
通讯作者：
Mi単arro, J
影响因子：
6.7
作者：
Dyer, KR;Foster, DJR;Bochner, F
通讯作者：
Bochner, F