Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran; Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.
Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran.
Behav Brain Res. 2022 Mar 12;421:113732. doi: 10.1016/j.bbr.2021.113732. Epub 2022 Jan 3.
Chronic morphine impairs cued fear extinction, which may contribute to the high prevalence of anxiety disorders and the replase of opiate addiction. This work investigated the effects of forced exercise with different intensities on cued fear extinction impairment and alternations of hippocampal BDNF and apoptotic proteins induced by chronic morphine. Rats were injected with bi-daily doses of morphine or saline for ten days and then received a cued or contextual fear conditioning training, which was followed by fear extinction training for four consecutive days. Cued, but the not contextual fear response was impaired in morphine-treated rats. Then, different saline or morphine-treated rats underwent forced exercise for 4-weeks with light, moderate or high intensities. Subsequently, rats received a cued fear conditioning followed by four days of extinction training, and the expression of hippocampal BDNF and apoptotic proteins was determined. A relatively long time after the last injection of morphine (35 days), rats again showed cued fear extinction failure and reduced hippocampal BDNF, which recovered by light and moderate, but not high exercise. Light and moderate, but not high-intensity treadmill exercise enhanced the up-regulation of Bcl-2 and down-regulation of the Bax proteins in both saline- and morphine-treated rats, which shifted the balance between pro-apoptotic and anti-apoptotic factors in favor of cell survival. These findings highlight the impact of exercise up to moderate intensity in the recovery of cued extinction failure, more likely via BDNF in addicted individuals.
慢性吗啡会损害条件恐惧消退，这可能导致焦虑障碍的高发和阿片类药物成瘾的复发。本工作研究了不同强度的强制运动对慢性吗啡诱导的条件恐惧消退障碍和海马 BDNF 及凋亡蛋白变化的影响。大鼠每天接受两次吗啡或生理盐水注射，持续十天，然后进行条件或情境恐惧条件训练，随后进行连续四天的恐惧消退训练。吗啡处理的大鼠表现出条件恐惧反应受损，但不表现出情境恐惧反应。然后，不同的生理盐水或吗啡处理的大鼠进行为期四周的轻、中、高强度强制运动。随后，大鼠接受条件恐惧条件训练，然后进行四天的消退训练，测定海马 BDNF 和凋亡蛋白的表达。在最后一次注射吗啡后相当长的时间（35 天），大鼠再次表现出条件恐惧消退失败和海马 BDNF 减少，而轻、中强度运动恢复了 BDNF，而高强度运动没有恢复。轻、中强度但不是高强度跑步机运动增强了生理盐水和吗啡处理的大鼠中 Bcl-2 的上调和 Bax 蛋白的下调，使促凋亡和抗凋亡因子之间的平衡有利于细胞存活。这些发现强调了运动至中等强度对恢复条件消退失败的影响，在成瘾个体中，更可能通过 BDNF 实现。
