DOPAMINE RELEASE AND METABOLISM IN NUCLEUS-ACCUMBENS AND STRIATUM OF MORPHINE-TOLERANT AND NONTOLERANT RATS
DOPAMINE RELEASE AND METABOLISM IN NUCLEUS-ACCUMBENS AND STRIATUM OF MORPHINE-TOLERANT AND NONTOLERANT RATS
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DOI：
10.1016/0091-3057(93)90362-w
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发表时间：
1993-10-01
影响因子：
3.6
通讯作者：
GLICK, SD
中科院分区：
文献类型：
--
作者：
JOHNSON, DW;GLICK, SD
高剂量的吗啡会产生一种双相运动效应，以最初的运动抑制为特征，随后是短时间的过度运动。预先接触吗啡会产生对运动抑制效应的耐受性，并对吗啡的运动激活效应产生敏化作用。对产生对吗啡的耐受性和敏感度的神经化学变化知之甚少。在本研究中，我们开发了一种对大鼠产生耐受性和对高剂量(30 mg/kg)吗啡敏感的吗啡预处理方案。采用体内微透析法测定吗啡和生理盐水处理大鼠急性给药后伏隔核(NAC)和纹状体(STR)多巴胺(DA)、二羟基苯乙酸(DOPAC)和高香草酸(HVA)的释放。吗啡耐受/致敏大鼠急性注射吗啡后，NAc区DA基础浓度升高，DOPAC和HVA含量升高。这些结果表明，NAC，而不是STR，可能在阿片类药物的耐受和增敏中起重要作用。
Morphine administered at high doses produces a biphasic locomotor effect, characterized by an initial locomotor depression, followed a short time later by hyperlocomotion. Prior exposure to morphine produces tolerance to the motor-depressive effects and sensitization to the motor-activating effects of morphine. Little is known of the neurochemical changes that occur to produce tolerance and sensitization to morphine. In the present study, we developed a morphine pretreatment regimen in rats that produced both tolerance and sensitization to a high (30 mg/kg) dose of morphine. Using in vivo microdialysis, we then measured dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) release in the nucleus accumbens (NAC) and striatum (STR) in morphine- and saline-pretreated rats after acute morphine administration. In morphine-tolerant/sensitized rats, basal DA concentrations in the NAC were higher and levels of DOPAC and HVA in the NAC after acute morphine injection were greater compared to controls. These results suggest that the NAC, but not the STR, may be important in mediating tolerance and sensitization to opiates.