Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats.
Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats.
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伏隔核中的二甲双胍可减少雄性和雌性大鼠的提示引起的可卡因。
作者：
本研究探讨了美国食品药品监督管理局（FDA）批准的药物二甲双胍对线索诱导的可卡因觅药行为复燃的潜在治疗效果。二甲双胍（二甲基双胍）是治疗II型糖尿病的一线药物，其作用机制包括激活腺苷酸活化蛋白激酶（AMPK）等。可卡因自我给药和消退与伏隔核核心（NAcore）内磷酸化AMPK水平降低有关。先前的研究表明，提高NAcore中的AMPK活性可减少线索诱导的可卡因觅药行为复燃，而降低AMPK活性则产生相反的效果。本研究的目的是确定在NAcore中使用二甲双胍是否能减少成年雄性和雌性斯普拉格 - 道利大鼠线索诱导的可卡因觅药行为。大鼠先接受可卡因自我给药训练，然后在进行线索诱导的复燃试验之前经历消退过程。在NAcore中微量注射二甲双胍可减轻雄性和雌性大鼠线索诱导的复燃行为。重要的是，二甲双胍对可卡因觅药行为的影响并非由于自发运动活性的普遍降低。在雌性大鼠中，二甲双胍的作用确实可推广到减少线索诱导的蔗糖觅药行为复燃。这些数据支持二甲双胍作为可卡因使用障碍的一种药物疗法的潜在作用，但鉴于二甲双胍的作用在雌性大鼠中可能推广到自然奖赏，应谨慎对待。
二甲双胍是一种已知可激活细胞能量传感器AMPK的II型糖尿病药物。先前已表明，在可卡因自我给药和消退后，磷酸化AMPK会降低。在此，我们报告在伏隔核核心微量注射二甲双胍可减少线索诱导的可卡因觅药行为复燃。
This study investigated the potential therapeutic effects of the FDA‐approved drug metformin on cue‐induced reinstatement of cocaine seeking. Metformin (dimethyl‐biguanide) is a first‐line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self‐administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously, it was shown that increasing AMPK activity in the NAcore decreased cue‐induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue‐induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self‐administer cocaine followed by extinction prior to cue‐induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue‐induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue‐induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats. Metformin is a type II diabetes drug known to activate the cellular energy sensor AMPK. It has previously been shown that phopsho‐AMPK is decreased after cocaine self‐administration and extinction. Here, we report that metformin microinjected in the nucleus accumbens core reduces cue‐induced reinstatement of cocaine seeking.
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影响因子：
4.2
作者：
Becker, Jill B.;McClellan, Michele L.;Reed, Beth Glover
通讯作者：
Reed, Beth Glover
影响因子：
2.1
作者：
Fatemi I;Amirteimoury M;Shamsizadeh A;Kaeidi A
通讯作者：
Kaeidi A
DOI：
10.1016/j.pnpbp.2018.01.002
发表时间：
2018-12-20
影响因子：
5.6
作者：
Farrell MR;Schoch H;Mahler SV
通讯作者：
Mahler SV
DOI：
10.3390/ph14020122
发表时间：
2021-02-05
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Drzewoski J;Hanefeld M
通讯作者：
Hanefeld M
影响因子：
6
作者：
Hoots, Brooke;Vivolo-Kantor, Alana;Seth, Puja
通讯作者：
Seth, Puja