Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains
Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains
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DOI：
10.1007/s00213-014-3826-5
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发表时间：
2015-06-01
影响因子：
3.4
通讯作者：
Lutz, P. -E.
中科院分区：
文献类型：
--
作者：
Ayranci, G.;Befort, K.;Lutz, P. -E.
阿片类药物成瘾是一种通过反复中毒和戒断发作而出现的大脑疾病。流行病学研究还表明，长期接触阿片类药物可能导致易受影响的人出现抑郁症状，这在很大程度上促成了成瘾的严重性和长期性。我们最近建立了一个海洛因戒断的小鼠模型，其特征是慢性海洛因暴露后抑郁样行为的发展，虽然调节阿片类药物即时行为反应的遗传因素已被大量研究，但对戒断期间长期情绪调节的贡献知之甚少。在这里，我们比较了不同遗传背景的小鼠品系（C57 BL/6 J，Balb/cByJ和129 S2/SvPas）的海洛因暴露引起的运动刺激和身体依赖，以及戒断后的情感功能障碍。独立的队列被用来评估药物诱导的自发活动在慢性治疗，纳洛酮沉淀戒断慢性治疗结束时，和情绪样反应后，4周的禁欲periods. Distinguished行为剖面海洛因治疗期间观察到跨株，没有身体依赖性和低运动刺激129 S2/SvPas。此外，3个品系在戒断过程中均出现不同程度的行为障碍，其中129 S2/SvPas和Balb/cByJ的绝望样行为增加，而129 S2/SvPas和C57 BL/6 J的社交能力降低。此外，近交系小鼠品系将允许研究与成瘾相关的情绪相关缺陷的几个方面。
Opiate addiction is a brain disorder emerging through repeated intoxication and withdrawal episodes. Epidemiological studies also indicate that chronic exposure to opiates may lead in susceptible individuals to the emergence of depressive symptoms, strongly contributing to the severity and chronicity of addiction. We recently established a mouse model of heroin abstinence, characterized by the development of depressive-like behaviors following chronic heroin exposure.While genetic factors regulating immediate behavioral responses to opiates have been largely investigated, little is known about their contribution to long-term emotional regulation during abstinence. Here, we compared locomotor stimulation and physical dependence induced by heroin exposure, as well as emotional dysfunction following abstinence, across mice strains with distinct genetic backgrounds.Mice from three inbred strains (C57BL/6J, Balb/cByJ, and 129S2/SvPas) were exposed to an escalating chronic heroin regimen (10-50 mg/kg). Independent cohorts were used to assess drug-induced locomotor activity during chronic treatment, naloxone-precipitated withdrawal at the end of chronic treatment, and emotional-like responses after a 4-week abstinence period.Distinct behavioral profiles were observed across strains during heroin treatment, with no physical dependence and low locomotor stimulation in 129S2/SvPas. In addition, different behavioral impairments developed during abstinence across the three strains, with increased despair-like behavior in 129S2/SvPas and Balb/cByJ, and low sociability in 129S2/SvPas and C57BL/6J.Our results indicate that depressive-like behaviors emerge during heroin abstinence, whatever the severity of immediate behavioral responses to the drug. In addition, inbred mouse strains will allow studying several aspects of mood-related deficits associated with addiction.