Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats.
Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats.
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DOI：
10.3389/fphar.2022.1082760
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发表时间：
2022
影响因子：
5.6
通讯作者：
Stevenson CW
中科院分区：
文献类型：
--
作者：
Warren WG;Papagianni EP;Hale E;Brociek RA;Cassaday HJ;Stevenson CW
内源性大麻素的传递正在成为治疗焦虑相关疾病的目标，因为它可以调节恐惧消退。通过脂肪酸酰胺水解酶（FAAH）抑制花生四烯酸酰胺的代谢来提高花生四烯酸酰胺的水平可以增强消光，而抑制单酰基甘油脂肪酶（MAGL）以提高2-花生四烯酸酰甘油的水平可以削弱消光。然而，内源性大麻素是否随着时间的推移调节恐惧复发或灭绝抵抗仍不清楚。在使用听觉恐惧条件化大鼠的两个实验中，我们检查了全身施用FAAH抑制剂URB 597和MAGL抑制剂JZL 184对1）延迟消退后的自发性恐惧恢复和2）由立即消退引起的消退抵抗[立即消退缺陷（IED）]的影响。在实验1中，URB 597或JZL 184后立即给予延迟消退发生后24小时条件反射。分别在无药物1天和21天后测试消退回忆和自发恐惧恢复。我们发现，这两种药物对消退记忆或自发性恐惧恢复都没有影响。实验2在条件反射后30 min立即消退前给予URB 597或JZL 184，次日进行无药物消退回忆测试。我们还研究了普萘洛尔的影响，β-肾上腺素受体拮抗剂，可以挽救IED，作为阳性对照。JZL 184增强了恐惧表达和受损的消退学习，但我们发现URB 597或JZL 184对线索消退回忆没有持久的影响。普萘洛尔减少了恐惧的表达，但出乎意料的是，对消退记忆没有持久的影响。研究结果进行了讨论，在以前的研究内源性大麻素和肾上腺素能调节的恐惧灭绝之间的各种方法的差异。
Endocannabinoid transmission is emerging as a target for treating anxiety-related disorders, given its regulation of fear extinction. Boosting anandamide levels via inhibition of its metabolism by fatty acid amide hydrolase (FAAH) can enhance extinction, whereas inhibiting monoacylglycerol lipase (MAGL) to elevate 2-arachidonoylglycerol levels can impair extinction. However, whether endocannabinoids regulate fear relapse over time or extinction resistance remains unclear. In two experiments using auditory fear conditioned rats, we examined the effects of the FAAH inhibitor URB597 and the MAGL inhibitor JZL184 administered systemically on 1) spontaneous fear recovery after delayed extinction, and 2) extinction resistance resulting from immediate extinction [the immediate extinction deficit (IED)]. In Experiment 1, URB597 or JZL184 was given immediately after delayed extinction occurring 24 h after conditioning. Extinction recall and spontaneous fear recovery were tested drug-free 1 and 21 days later, respectively. We found no effects of either drug on extinction recall or spontaneous fear recovery. In Experiment 2, URB597 or JZL184 was given before immediate extinction occurring 30 min after conditioning and extinction recall was tested drug-free the next day. We also examined the effects of propranolol, a beta-adrenoceptor antagonist that can rescue the IED, as a positive control. JZL184 enhanced fear expression and impaired extinction learning but we found no lasting effects of URB597 or JZL184 on cued extinction recall. Propranolol reduced fear expression but, unexpectedly, had no enduring effect on extinction recall. The results are discussed in relation to various methodological differences between previous studies examining endocannabinoid and adrenergic regulation of fear extinction.
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影响因子：
4.7
作者：
Warren, William G.;Hale, Ed;Papagianni, Eleni P.;Cassaday, Helen J.;Stevenson, Carl W.;Stubbendorff, Christine
通讯作者：
Stubbendorff, Christine
DOI：
10.1126/science.1214592
发表时间：
2011-12-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Karpova NN;Pickenhagen A;Lindholm J;Tiraboschi E;Kulesskaya N;Agústsdóttir A;Antila H;Popova D;Akamine Y;Bahi A;Sullivan R;Hen R;Drew LJ;Castrén E
通讯作者：
Castrén E
2-芳基烯丙基甘油信号传导会损害短期恐惧灭绝。
影响因子：
6.8
作者：
Hartley ND;Gunduz-Cinar O;Halladay L;Bukalo O;Holmes A;Patel S
通讯作者：
Patel S
影响因子：
3.6
作者：
Hasanein, Parisa;Far, Massoud Teimuri
通讯作者：
Far, Massoud Teimuri
影响因子：
7.6
作者：
Giustino, Thomas F.;Seemann, Jocelyn R.;Maren, Stephen
通讯作者：
Maren, Stephen