Dysregulation in glucocorticoid stress and accumbal dopamine reward systems can alter reward salience to increase motivational drive in control conditions while contributing to relapse during drug withdrawal. Amphetamine withdrawal is associated with dysphoria and stress hypersensitivity that may be mediated, in part, by enhanced stress-induced corticosterone observed in the ventral hippocampus. Electrical stimulation of the ventral hippocampus enhances accumbal shell dopamine release, establishing a functional connection between these two regions. However, the effects of ventral hippocampal corticosterone on this system are unknown. To address this, a stress-relevant concentration of corticosterone (0.24ng/0.5 μL) or vehicle were infused into the ventral hippocampus of urethane-anesthetized adult male rats in control and amphetamine withdrawn conditions. Accumbal dopamine output was assessed with in vivo chronoamperometry. Corticosterone infused into the ventral hippocampus rapidly enhanced accumbal dopamine output in control conditions, but produced a biphasic reduction of accumbal dopamine output in amphetamine withdrawal. Selectively blocking glucocorticoid-, mineralocorticoid-, or cytosolic receptors prevented the effects of corticosterone. Overall, these results suggest that the ability of corticosterone to alter accumbal dopamine output requires cooperative activation of mineralocorticoid and glucocorticoid receptors in the cytosol, which is dysregulated during amphetamine withdrawal. These findings implicate ventral hippocampal corticosterone in playing an important role in driving neural systems involved in positive stress coping mechanisms in healthy conditions, whereas dysregulation of this system may contribute to relapse during withdrawal.

中文翻译：

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腹侧海马中的皮质酮有差异地改变了未用药和撤除苯丙胺的大鼠的累积多巴胺输出。

糖皮质激素应激和累积的多巴胺奖赏系统失调可以改变奖赏显着性，从而增加控制条件下的动机驱动力，同时有助于停药期间的复发。苯丙胺戒断与烦躁不安和压力超敏反应有关，其可能部分由在腹侧海马中观察到的应激诱导的皮质酮增强引起。腹侧海马的电刺激增强了shell壳多巴胺的释放，在这两个区域之间建立了功能连接。然而，腹侧海马皮质酮对该系统的作用尚不清楚。为了解决这个问题，皮质酮的应力相关浓度为（0.24ng / 0。在对照和苯丙胺撤除条件下，将5μL（L）或溶媒注入尿烷麻醉的成年雄性大鼠的腹侧海马中。用体内计时电流法评估累积的多巴胺输出量。在对照条件下，注入腹侧海马的皮质酮迅速增加了累积的多巴胺输出，但是在苯丙胺戒断时却产生了双相的累积的多巴胺输出减少。选择性地阻断糖皮质激素，盐皮质激素或细胞溶质的受体阻止了皮质酮的作用。总体而言，这些结果表明，皮质酮改变伏安性多巴胺输出的能力需要细胞溶质中盐皮质激素和糖皮质激素受体的协同激活，在苯丙胺戒断过程中这种受体失调。