The oxytocin analogue carbetocin prevents priming-induced reinstatement of morphine-seeking: Involvement of dopaminergic, noradrenergic and MOPr systems
The oxytocin analogue carbetocin prevents priming-induced reinstatement of morphine-seeking: Involvement of dopaminergic, noradrenergic and MOPr systems
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DOI：
10.1016/j.euroneuro.2015.09.015
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发表时间：
2015-12-01
影响因子：
5.6
通讯作者：
Bailey, Alexis
中科院分区：
文献类型：
--
作者：
Georgiou, Polymnia;Zanos, Panos;Bailey, Alexis
由于没有有效的药物治疗方法，戒断后再次寻求非法药物是治疗成瘾的主要挑战。我们最近的研究表明，激活中枢催产素系统可以防止与阿片类药物戒断相关的情绪损害和压力诱导的恢复。在这里，我们研究了催产素类似物卡贝菌素（CBT）是否能够逆转吗啡引发的小鼠条件位置偏好（CPP）的恢复。通过评估纹状体去肾上腺素能和多巴胺能系统参与CBT逆转启动和应激诱导的阿片类药物CPP恢复的机制，研究了CBT行为效应的机制。此外，鉴于最近的证据表明催产素受体(OTR)-mu-阿片受体（MOPr）在大脑中存在相互作用，我们通过在缺乏MOPr的小鼠大脑中进行OTR放射自显影结合来进一步探索这些相互作用。CBT可阻止启动诱导的吗啡心肺复苏术恢复。在应激和启动诱导的复苏术中，CBT可显著增强多巴胺转换，但CBT仅能显著降低启动诱导的复苏术纹状体去甲肾上腺素转换。此外，在MOPr敲除小鼠中观察到OTR结合显著的脑区特异性增加，表明可能存在or -MOPr相互作用，这可能参与了复发的调节。这些结果支持了催产素系统作为预防阿片类药物使用复发的有希望的目标，并强调了单胺能系统在OTR刺激预防应激和启动诱导的阿片类药物CPP行为恢复中的不同参与。(C) 2015 Elsevier B.V.和ECNP。版权所有。
Relapse to illicit drug-seeking following abstinence is a major challenge for the treatment of addiction as no effective pharmacotherapy is available. We have recently shown that activating the central oxytocinergic system prevents emotional impairment and stress-induced reinstatement associated with opioid withdrawal. Here, we investigated whether the oxytocin analogue carbetocin (CBT) is able to reverse morphine-primed reinstatement of conditioned-place preference (CPP) in mice. The mechanism underlining the behavioural effect of CBT was investigated by assessing the involvement of the striatal noradrenergic and dopaminergic systems in CBT reversal of priming- and stress-induced reinstatement of opioid CPP. In addition, given recent evidence suggesting the presence of oxytocin receptor (OTR)-mu-opioid receptor (MOPr) interactions in the brain, we further explored these interactions by carrying out OTR autoradiographic binding in brain of mice lacking MOPr. CBT administration prevented priminginduced reinstatement of morphine CPR While an acute effect of CBT in enhancing dopamine turnover was observed following stress- and priming-induced reinstatement, CBT significantly decreased striatal noradrenaline turnover only following priming-induced reinstatement. Moreover, a significant brain region- specific increase in OTR binding was observed in MOPr knockout mice, indicating the presence of a possible OTR-MOPr interaction, which may be involved in the modulation of relapse. These results support the oxytocinergic system as a promising target for the prevention of relapse to opioid use and highlight the differential involvement of monoaminergic systems on the effects of OTR stimulation in preventing stressand priming-induced reinstatement of opioid CPP behaviour. (C) 2015 Elsevier B.V. and ECNP. All rights reserved.