Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate-putamen in rats sensitized to morphine
Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate-putamen in rats sensitized to morphine
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DOI：
10.1016/s0306-4522(98)00466-7
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发表时间：
1999-05-01
期刊：
影响因子：
3.3
通讯作者：
Di Chiara, G
中科院分区：
文献类型：
--
作者：
Cadoni, C;Di Chiara, G
在这项研究中，我们描述了一种阿片类药物致敏模型，其特征是重复吗啡给药的简短治疗方案。在该模型中，我们研究了废除吗啡治疗对两个主要末端多巴胺能区域水平的多巴胺传递产生的变化，即背外侧尾壳核和伏核的两个细分部分（壳和核）。连续三天每天两次用递增剂量的吗啡（10、20 和 40 mg/kg，皮下注射）或盐水对大鼠进行治疗。停药 15 天后，大鼠接受 1 和 5 mg/kg（皮下）吗啡攻击，并通过微透析监测多巴胺传输。在该模型中，我们发现，与对照大鼠相比，重复吗啡会产生强烈的行为敏化，伴随着伏隔核核心和尾壳核中多巴胺传递的刺激增加，以及伏隔核壳中多巴胺传递的刺激减少。此外，我们给这些动物施用安非他明（0.5 mg/kg，皮下注射）和可卡因（10 mg/kg，腹腔注射），以评估在独立于环境的条件下阿片类药物和精神兴奋剂之间是否发生交叉过敏。在本研究中，我们没有观察到对吗啡敏感的大鼠对安非他明和可卡因的行为或生化过敏。这些结果表明，对吗啡敏感的大鼠在伏隔核壳和核以及背侧尾壳核中吗啡的刺激作用表现出相反的变化。此外，这项研究表明多巴胺系统对给定药物的过敏并不一定延伸到药物不同药理学类别的滥用。 (C) 1999 国际广播组织。由爱思唯尔科学有限公司出版
In this study, we describe a model of opiate sensitization characterized by a brief schedule of treatment with repeated morphine administrations. In this model, we investigated the changes produced by repealed morphine treatment on dopamine transmission at the level of the two major terminal dopaminergic areas, the dorsolateral caudate-putamen and the nucleus accumbens in its two subdivisions, the shell and the core. Rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with 1 and 5 mg/kg (s.c.) of morphine, and dopamine transmission was monitored by microdialysis. In this model, we show that repeated morphine produces a strong behavioral sensitization accompained by increased stimulation of dopamine transmission in the core of the nucleus accumbens and in the caudate-putamen, and by a decreased stimulation of dopamine transmission in the shell of the nucleus accumbens, as compared to control rats. Moreover, we administered to these animals amphetamine (0.5 mg/kg, s.c.) and cocaine (10 mg/kg, i.p.) to assess whether cross-sensitization occurs between opiates and psychostimulants in conditions independent of the context. In the present study, we did not observe either behavioral or biochemical sensitization to amphetamine and to cocaine in rats sensitized to morphine.These results suggest that rats behaviorally sensitized to morphine show opposite changes in the stimulant effect of morphine in the nucleus accumbens shell and core and in the dorsal caudate-putamen, Moreover, this study suggests that sensitization of the dopamine system to a given agent does not necessarily extend to drugs of abuse of different pharmacological classes. (C) 1999 IBRO. Published by Elsevier Science Ltd.