Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bengaluru, 560 029, India.
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bengaluru, 560 029, India.
Brain Stimul. 2019 May-Jun;12(3):752-766. doi: 10.1016/j.brs.2019.01.020. Epub 2019 Jan 31.
Major depressive disorder (MDD) is a multifactorial disease which often coexists with cognitive deficits. Depression-induced cognitive deficits are known to be associated with aberrant reward processing, neurochemical and structural alterations. Recent studies have shown that chronic electrical stimulation of brain reward areas induces a robust antidepressant effect. However, the effects of repeated electrical self-stimulation of lateral hypothalamus - medial forebrain bundle (LH-MFB) on depression-induced cognitive deficits and associated neurochemical and structural alterations in the prefrontal cortex (PFC) are unknown.
We investigated the effect of chronic rewarding self-stimulation of LH-MFB in neonatal clomipramine (CLI) model of depression. During adulthood, neonatal CLI and saline administered rats were implanted with bilateral electrodes stereotaxically in the LH-MFB and trained to receive intracranial self-stimulation (ICSS) for 14 days. The rats were tested for depressive-like behaviors, learning and memory followed by estimation of PFC volumes, levels of monoamines and its metabolites in the PFC.
We found that chronic ICSS of LH-MFB reverses CLI-induced behavioral despair and anhedonia. Interestingly, self-stimulation normalizes the impaired novel object and location recognition memory in CLI rats. The amelioration of learning impairments in CLI rats was associated with the reversal of volume loss and restoration of monoamine metabolism in the PFC.
We demonstrated that repeated intracranial self-stimulation of LH-MFB ameliorates CLI-induced learning deficits, reverses altered monoamine metabolism and the atrophy of PFC. Our results support the hypothesis that chronic brain stimulation rewarding experience might be evolved as a potential treatment strategy for reversal of learning deficits in depression and associated disorders.
重度抑郁症（MDD）是一种多因素疾病，常伴有认知缺陷。已知抑郁引起的认知缺陷与异常的奖励处理、神经化学和结构改变有关。最近的研究表明，大脑奖励区域的慢性电刺激会产生强大的抗抑郁作用。然而，反复电刺激外侧下丘脑-中脑束（LH-MFB）对抑郁引起的认知缺陷以及前额叶皮层（PFC）中相关的神经化学和结构改变的影响尚不清楚。
我们研究了慢性奖赏性 LH-MFB 刺激对新生氯丙咪嗪（CLI）抑郁模型的影响。在成年期，新生 CLI 和生理盐水给药的大鼠通过立体定向双侧电极植入 LH-MFB 并接受 14 天的颅内自我刺激（ICSS）训练。大鼠接受抑郁样行为、学习和记忆测试，随后评估 PFC 体积、PFC 中单胺及其代谢物的水平。
我们发现，慢性 LH-MFB-ICSS 可逆转 CLI 诱导的行为绝望和快感缺失。有趣的是，自我刺激使 CLI 大鼠受损的新物体和位置识别记忆正常化。CLI 大鼠学习障碍的改善与 PFC 体积损失的逆转和单胺代谢的恢复有关。
我们证明了反复 LH-MFB 颅内自我刺激可改善 CLI 诱导的学习障碍，逆转改变的单胺代谢和 PFC 萎缩。我们的研究结果支持了这样一种假设，即慢性大脑刺激奖励体验可能演变为逆转抑郁和相关障碍中学习障碍的潜在治疗策略。
