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Naloxone-precipitated withdrawal ameliorates impairment of cost-benefit decision making in morphine-treated rats: Involvement of BDNF, p-GSK3-β, and p-CREB in the amygdala.
Neurobiology of Learning and Memory ( IF 2.2 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.nlm.2019.107138
Zahra Fatahi 1 , Arman Zeinaddini-Meymand 2 , Saeideh Karimi-Haghighi 1 , Marzieh Moradi 3 , Fariba Khodagholi 1 , Abbas Haghparast 1
Affiliation  

Several studies indicated that morphine administration impairs cognitive brain functions. Therefore, in the current study, we investigated the effect of subchronic exposure to morphine and its withdrawal on effort- and/or delay-based forms of cost-benefit decision making and alterations in p-CREB/CREB ratio, p-GSK3β/GSK3β ratio, and BDNF level during decision making in the amygdala. Our data displayed an impairment of both forms of cost-benefit decision making following subchronic exposure to morphine. However, preference of high reward/high effort and/or high delay reward increased after naloxone injection. In molecular section, levels of BDNF and p-CREB/CREB ratio increased during cost-benefit decision making while p-GSK3β/GSK3β ratio decreased in both forms of decision making. In morphine-treated rats, level of BDNF and p-CREB/CREB ratio reduced during both forms of decision making while p-GSK3β/GSK3β ratio increased during delay-based and did not have a significant difference with the control group during effort-based decision making. On the withdrawal day, BDNF level raised while p-GSK3β/GSK3β ratio attenuated compared to morphine-treated group in both form of decision making. In addition, p-CREB/CREB ratio increased only during delay-based decision making on the withdrawal day. In conclusion, our data revealed that subchronic exposure to morphine interferes with the cost-benefit decision making may be via changes in level of BDNF, p-CREB/CREB and p-GSK3β/GSK3β ratio in the amygdala.

中文翻译:


纳洛酮促使戒断改善吗啡治疗大鼠的成本效益决策受损:杏仁核中 BDNF、p-GSK3-β 和 p-CREB ​​的参与。



多项研究表明吗啡给药会损害大脑认知功能。因此,在本研究中,我们研究了吗啡亚慢性暴露及其戒断对基于努力和/或延迟形式的成本效益决策的影响以及 p-CREB/CREB ​​比率、p-GSK3β/GSK3β 的变化比率和杏仁核决策过程中的 BDNF 水平。我们的数据显示,亚慢性接触吗啡后,这两种形式的成本效益决策都会受到损害。然而,注射纳洛酮后,对高奖励/高努力和/或高延迟奖励的偏好增加。在分子部分,BDNF 水平和 p-CREB/CREB ​​比率在成本效益决策过程中增加,而 p-GSK3β/GSK3β 比率在两种形式的决策过程中下降。在吗啡治疗的大鼠中,在两种形式的决策过程中 BDNF 水平和 p-CREB/CREB ​​比值均降低,而 p-GSK3β/GSK3β 比值在基于延迟的过程中增加,并且在基于努力的过程中与对照组没有显着差异决策。在停药当天,在两种决策形式中,与吗啡治疗组相比,BDNF 水平升高,而 p-GSK3β/GSK3β 比率减弱。此外,p-CREB/CREB ​​比率仅在停药日基于延迟的决策期间增加。总之,我们的数据表明,亚慢性暴露于吗啡会干扰成本效益决策,可能是通过杏仁核中 BDNF、p-CREB/CREB ​​和 p-GSK3β/GSK3β 比率的变化来实现的。
更新日期:2019-12-13
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