Bhagya V, Srikumar B N, Raju T R, Shankaranarayana Rao B S
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
J Neurosci Res. 2015 Jan;93(1):104-20. doi: 10.1002/jnr.23473. Epub 2014 Aug 21.
Depression is a major psychiatric illness that is associated with cognitive dysfunctions. The underlying mechanism of depression-associated memory impairment is unclear. Previously, we showed altered hippocampal synaptic plasticity in an animal model of depression. Although several antidepressants are beneficial in the treatment of depression, very little is known about the effects of these drugs on depression-associated learning and memory deficits. Prolonged antidepressant treatment might contribute to neuroplastic changes required for clinical outcomes. Accordingly, we evaluated the effect of chronic reboxetine (a selective noradrenergic reuptake inhibitor) treatment on depression-induced reduced hippocampal synaptic plasticity, neurotransmitter levels, and spatial learning and memory impairments. Depression was induced in male Wistar rats by the administration of clomipramine from postnatal days 8 to 21, and these rats were treated with reboxetine in adulthood. The neonatal clomipramine administration resulted in impaired hippocampal long-term potentiation (LTP), decreased hippocampal cholinergic activity and monoamine levels, and poor performance in a partially baited eight-arm radial maze task. Chronic reboxetine treatment restored the hippocampal LTP, acetylcholinesterase activity, and levels of biogenic amines and ameliorated spatial learning and memory deficits in the depressed state. Thus, restoration of hippocampal synaptic plasticity might be a cellular mechanism underlying the beneficial effect of reboxetine in depression-associated cognitive deficits. This study furthers the existing understanding of the effects of antidepressants on learning, memory, and synaptic plasticity and could ultimately assist in the development of better therapeutic strategies to treat depression and associated cognitive impairments.
抑郁症是一种与认知功能障碍相关的主要精神疾病。抑郁症相关记忆损害的潜在机制尚不清楚。此前，我们在抑郁症动物模型中发现海马突触可塑性发生改变。尽管几种抗抑郁药对抑郁症治疗有益，但对于这些药物对抑郁症相关学习和记忆缺陷的影响知之甚少。长期抗抑郁治疗可能有助于产生临床疗效所需的神经可塑性变化。因此，我们评估了慢性瑞波西汀（一种选择性去甲肾上腺素再摄取抑制剂）治疗对抑郁症诱导的海马突触可塑性降低、神经递质水平以及空间学习和记忆损害的影响。通过在出生后第8天至21天给予氯米帕明诱导雄性Wistar大鼠患抑郁症，这些大鼠在成年后接受瑞波西汀治疗。新生儿期给予氯米帕明导致海马长时程增强（LTP）受损、海马胆碱能活性和单胺水平降低，以及在部分诱饵八臂放射状迷宫任务中的表现不佳。慢性瑞波西汀治疗恢复了海马LTP、乙酰胆碱酯酶活性、生物胺水平，并改善了抑郁状态下的空间学习和记忆缺陷。因此，恢复海马突触可塑性可能是瑞波西汀对抑郁症相关认知缺陷产生有益作用的细胞机制。本研究进一步加深了我们对抗抑郁药对学习、记忆和突触可塑性影响的现有认识，并最终可能有助于开发更好的治疗策略来治疗抑郁症及相关认知障碍。
