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苯环己哌啶会影响与老鼠的奖励和社交行为相关的腹侧被盖区神经元的放电活动。

Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats.

机构信息

Department of Neurophysiology, School of Medicine, Fukushima Medical University, Fukushima City, Fukushima 960-1295, Japan.

出版信息

Neuroscience. 2013 Jun 14;240:336-48. doi: 10.1016/j.neuroscience.2013.02.047. Epub 2013 Mar 1.

Abstract

Patients with schizophrenia exhibit deficits in motivation and affect, which suggests an impairment in the reward system. The psychotomimetic drug, phencyclidine (PCP), also induces schizophrenia-like negative symptoms, such as reduced motivation, blunted affect, and social withdrawal in both humans and animals. Previous studies have indicated that the dopaminergic neurons in the ventral tegmental area (VTA) play a pivotal role in the development of reward-associated learning and motivation. However, how PCP affects the activity of VTA neurons during performance of a reward-related task and social interaction with others in unanesthetized animals remains unclear. Here, we recorded the unit activity of VTA neurons in freely moving rats before and after systemic administration of PCP in a classical conditioning paradigm, and during social interaction with an unfamiliar partner. In the classical conditioning task, two different tones were sequentially presented, one of which accompanied electrical stimulation of the medial forebrain bundle as an unconditioned stimulus. After identifying the response properties of recorded neurons in the classical conditioning task and social interaction, animals received an intraperitoneal injection of PCP. Our study demonstrated that most VTA neurons responsive to reward-associated stimuli were also activated during social interaction. Such activation of neurons was considerably suppressed by systemic administration of PCP, thus, PCP may affect the firing activity of VTA neurons that are involved in motivation, learning, and social interaction. Disruption of the response of VTA neurons to reward stimuli and socially interactive situations may be involved in PCP-induced impairments similar to the negative symptoms of schizophrenia.

摘要

精神分裂症患者表现出动机和情感缺陷,这表明他们的奖励系统受损。致幻药物苯环利定(PCP)也会在人类和动物中引起类似精神分裂症的阴性症状,如动机降低、情感迟钝和社交退缩。先前的研究表明,腹侧被盖区(VTA)中的多巴胺能神经元在奖励相关学习和动机的发展中起着关键作用。然而,PCP 如何影响未麻醉动物在执行与奖励相关的任务和与他人进行社交互动时 VTA 神经元的活动仍不清楚。在这里,我们在经典条件反射范式中,在全身给予 PCP 之前和之后,在自由活动的大鼠中记录 VTA 神经元的单位活动,并且在与不熟悉的伙伴进行社交互动期间记录 VTA 神经元的单位活动。在经典条件反射任务中,两个不同的音调相继呈现,其中一个音调伴随着内侧前脑束的电刺激作为非条件刺激。在确定了记录神经元在经典条件反射任务和社交互动中的反应特性后,动物接受了 PCP 的腹腔注射。我们的研究表明,大多数对奖励相关刺激有反应的 VTA 神经元在社交互动中也被激活。全身给予 PCP 可显著抑制这种神经元的激活,因此,PCP 可能会影响 VTA 神经元的放电活动,而 VTA 神经元参与动机、学习和社交互动。VTA 神经元对奖励刺激和社交互动情况的反应中断可能与 PCP 引起的类似于精神分裂症阴性症状的损伤有关。

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