Differential adaptive properties of accumbens shell dopamine responses to ethanol as a drug and as a motivational stimulus
Differential adaptive properties of accumbens shell dopamine responses to ethanol as a drug and as a motivational stimulus
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DOI：
10.1046/j.1460-9568.2003.02556.x
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发表时间：
2003-04-01
影响因子：
3.4
通讯作者：
Di Chiara, G
中科院分区：
文献类型：
--
作者：
Bassareo, V;De Luca, MA;Di Chiara, G
药物滥用对伏隔核壳多巴胺传递的非适应性激活在药物成瘾机制中起着重要作用。为了验证这一假设，我们在同一受试者中比较了成瘾药物（乙醇）和味觉刺激（包括乙醇本身的味道）对伏隔核壳中透析多巴胺（多巴胺传递的估计）和味觉反应（动机效价的表达）的影响。透析液中的乙醇也被监测。在初生大鼠中，口服输注20%蔗糖+巧克力溶液引起透析液多巴胺在口服输注后立即单相增加。相比之下，口服输注10%乙醇、10%乙醇+ 20%蔗糖或10%乙醇+ 20%蔗糖+巧克力溶液引起伏隔核多巴胺双相增加，早期与味觉相关，晚期与透析乙醇相关。暴露于乙醇溶液24小时前，早期多巴胺升高消失，晚期多巴胺升高持续。当测试含有蔗糖的乙醇溶液时，与未预先接触的组相比，这种晚期多巴胺的增加实际上有所增加。结果表明，单次试验预暴露乙醇溶液对伏隔核壳多巴胺对乙醇直接脑内作用的反应性和对其味道的影响有不同的影响，或前者没有变化，后者消失。这些观察结果表明，与味觉奖励相比，药物后伏隔核壳内多巴胺传递的适应性调节存在重大差异。反过来，这些差异与伏隔核壳多巴胺在成瘾药物的行为影响机制中的作用是一致的。
Non-adaptive activation of dopamine transmission in the nucleus accumbens shell by drugs of abuse has been attributed a fundamental role in the mechanism of drug addiction. In order to test this hypothesis, we compared in the same subject the effect of an addictive drug (ethanol) and of taste stimuli, including ethanol's own taste, on dialysate dopamine in the nucleus accumbens shell as an estimate of dopamine transmission and on taste reactivity as an expression of motivational valence. Ethanol was also monitored in the dialysates. In naive rats, intraoral infusion of a 20% sucrose + chocolate solution elicited a monophasic increase of dialysate dopamine immediately after the intraoral infusion. In contrast, intraoral infusion of 10% ethanol, 10% ethanol + 20% sucrose or 10% ethanol + 20% sucrose + chocolate solutions elicited a biphasic increase of nucleus accumbens dopamine with an early taste-related rise and a late rise related to dialysate ethanol. Pre-exposure to the ethanol solutions 24 h before resulted in the absence of the early dopamine rise and permanence of the late dopamine rise. This late dopamine rise was actually increased as compared with that of the nonpre-exposed group when sucrose-containing ethanol solutions were tested. The results indicate that single trial pre-exposure to the ethanol solutions differentially affects the responsiveness of nucleus accumbens shell dopamine to the direct intracerebral action of ethanol and to the effect of its taste with potentiation, or no change of the first and abolition of the second. These observations point to the existence of major differences in the adaptive regulation of nucleus accumbens dopamine transmission in the shell after drug as compared with taste reward. These differences, in turn, are consistent with a role of nucleus accumbens shell dopamine in the mechanism of the behavioural effects of addictive drugs.