Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance.
Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance.
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大麻二酚可防止灭绝后自发的恐惧恢复，并改善压力诱导的灭绝耐药性。
DOI：
10.3390/ijms23169333
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发表时间：
2022-08-19
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
Cannabidiol是大麻的主要非精神成分，具有治疗焦虑相关疾病的潜力，因为它减少了学习恐惧的表达并增强了恐惧的消退。成功消退后随着时间的推移恐惧的回归和压力诱导的消退抵抗是以预防为基础的心理治疗治疗这些疾病的潜在障碍。在两个实验中，使用接受听觉恐惧条件反射的大鼠，我们确定了全身性大麻二酚治疗对（1）延迟消退和后来的自发性恐惧恢复的影响，以及（2）由立即消退引起的消退阻力（立即消退缺陷（IED））。在实验1中，大麻二酚之前，延迟灭绝发生后24小时条件反射，灭绝回忆和自发性恐惧恢复测试无药后1和21天，分别。我们发现大麻二酚对消退记忆没有影响，但它阻止了自发的恐惧恢复。在实验2中，首先验证IED程序，在调节后30分钟立即熄灭。我们证实，与延迟消退相比，立即消退损害了消退回忆。接下来，在立即或没有灭绝之前给予大麻二酚，第二天进行了无药物的灭绝回忆测试。我们发现大麻二酚拯救了IED，这并不涉及对恐惧记忆巩固的影响。总之，大麻二酚防止延迟消退后的自发性恐惧恢复，并改善由立即消退引起的消退抵抗力。虽然这些作用的药理学机制仍有待确定，但我们的研究结果增加了证据，表明大麻二酚可能被证明是有用的，可作为增强焦虑相关疾病的心理治疗的辅助手段。
Cannabidiol, the main non-psychotropic constituent of cannabis, has potential as a treatment for anxiety-related disorders since it reduces learned fear expression and enhances fear extinction. The return of fear over time after successful extinction and stress-induced extinction resistance are potential barriers to the treatment of these disorders with extinction-based psychological therapy. In two experiments using rats subjected to auditory fear conditioning, we determined the effects of systemic cannabidiol treatment on (1) delayed extinction and later spontaneous fear recovery, and (2) extinction resistance caused by immediate extinction (the immediate extinction deficit (IED)). In Experiment 1, cannabidiol was given before delayed extinction occurring 24 h after conditioning, with extinction recall and spontaneous fear recovery tested drug-free 1 and 21 days after extinction, respectively. We found that cannabidiol had no effect on extinction recall but it prevented spontaneous fear recovery. In Experiment 2, the IED procedure was first validated, with immediate extinction occurring 30 min after conditioning. We confirmed that immediate extinction impaired extinction recall, compared to delayed extinction. Next, cannabidiol was given before immediate or no extinction, with extinction recall tested drug-free the next day. We found that cannabidiol rescued the IED, which did not involve effects on fear memory consolidation. In summary, cannabidiol prevented spontaneous fear recovery after delayed extinction and ameliorated extinction resistance caused by immediate extinction. Although the pharmacological mechanisms underlying these effects remain to be determined, our results add to evidence indicating that cannabidiol might prove useful as an adjunct for potentiating the psychological treatment of anxiety-related disorders.
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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
压力下无情的恐惧：立即灭绝缺陷的神经回路和机制。
影响因子：
3
作者：
Maren, Stephen
通讯作者：
Maren, Stephen
影响因子：
7.6
作者：
Giustino, Thomas F.;Seemann, Jocelyn R.;Maren, Stephen
通讯作者：
Maren, Stephen
影响因子：
3.4
作者：
Hollis F;Sevelinges Y;Grosse J;Zanoletti O;Sandi C
通讯作者：
Sandi C
影响因子：
7.6
作者：
Atsak, Piray;Hauer, Daniela;Roozendaal, Benno
通讯作者：
Roozendaal, Benno