Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats
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DOI：
10.1038/s41386-018-0171-0
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发表时间：
2019-01-01
影响因子：
7.6
通讯作者：
Fone, Kevin C. F.
中科院分区：
文献类型：
--
作者：
Kohli, Shivali;King, Madeleine V.;Fone, Kevin C. F.
垂体神经肽催产素促进社会行为，是一种潜在的辅助治疗精神分裂症和自闭症的社会缺陷。催产素可以通过调节边缘系统和皮质区域中的单胺释放来介导亲社会效应，这在本文中使用体内微透析进行了研究，在建立了不产生伴随的镇静或体温调节效应的剂量后，可以伴随地影响行为。使用选择性拮抗剂测定催产素和加压素V-1a受体的作用，在成年雄性Lister-hooded大鼠中研究了催产素（0.03-0.3 mg/kg皮下注射）对自发活动、核心体温和社会行为（社会互动和超声发声）的影响。采用微透析技术研究清醒大鼠前额叶皮层和丘脑核多巴胺和5-羟色胺的流出。0.3 mg/kg催产素适度降低活动并引起体温降低，但只有后者被V-1a受体拮抗剂SR 49059（1 mg/kg腹腔内）减弱。催产素在0.1毫克/公斤，这并没有改变活动和对温度的影响很小，显着衰减苯环己哌啶诱导的多动症和增加不熟悉的大鼠之间的社会互动，而不改变超声波发声的数量或模式。在相同的大鼠中，催产素（0.1毫克/公斤）选择性地提高多巴胺溢出的丘脑核，但不前额叶皮层，不影响5-羟色胺流出。全身催产素给药减弱苯环利定诱导的多动和增加亲社会行为，而不降低核心体温和选择性地增强丘脑核多巴胺释放，与调节相关/奖励行为的中皮质边缘回路的激活一致。这突出了催产素治疗精神疾病（如精神分裂症）中的社会行为缺陷的治疗潜力。
The pituitary neuropeptide oxytocin promotes social behavior, and is a potential adjunct therapy for social deficits in schizophrenia and autism. Oxytocin may mediate pro-social effects by modulating monoamine release in limbic and cortical areas, which was investigated herein using in vivo microdialysis, after establishing a dose that did not produce accompanying sedative or thermoregulatory effects that could concomitantly influence behavior. The effects of oxytocin (0.03-0.3 mg/kg subcutaneous) on locomotor activity, core body temperature, and social behavior (social interaction and ultrasonic vocalizations) were examined in adult male Lister-hooded rats, using selective antagonists to determine the role of oxytocin and vasopressin V-1a receptors. Dopamine and serotonin efflux in the prefrontal cortex and nucleus accumbens of conscious rats were assessed using microdialysis. 0.3 mg/kg oxytocin modestly reduced activity and caused hypothermia but only the latter was attenuated by the V-1a receptor antagonist, SR49059 (1 mg/kg intraperitoneal). Oxytocin at 0.1 mg/kg, which did not alter activity and had little effect on temperature, significantly attenuated phencyclidine-induced hyperactivity and increased social interaction between unfamiliar rats without altering the number or pattern of ultrasonic vocalizations. In the same rats, oxytocin (0.1 mg/kg) selectively elevated dopamine overflow in the nucleus accumbens, but not prefrontal cortex, without influencing serotonin efflux. Systemic oxytocin administration attenuated phencyclidine-induced hyperactivity and increased pro-social behavior without decreasing core body temperature and selectively enhanced nucleus accumbens dopamine release, consistent with activation of mesocorticolimbic circuits regulating associative/reward behavior being involved. This highlights the therapeutic potential of oxytocin to treat social behavioral deficits seen in psychiatric disorders such as schizophrenia.