COCAINE-INDUCED CONDITIONED LOCOMOTION - ABSENCE OF ASSOCIATED INCREASES IN DOPAMINE RELEASE
COCAINE-INDUCED CONDITIONED LOCOMOTION - ABSENCE OF ASSOCIATED INCREASES IN DOPAMINE RELEASE
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DOI：
10.1016/0306-4522(92)90406-r
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发表时间：
1992-06-01
期刊：
影响因子：
3.3
通讯作者：
FIBIGER, HC
中科院分区：
文献类型：
--
作者：
BROWN, EE;FIBIGER, HC
可卡因的强有力的强化作用很容易与获得次级强化特性的显著环境刺激相关联。这种现象具有相当大的意义，因为强烈的渴望可以被先前与可卡因效应相关的刺激所诱发。有人提出，这些条件刺激的强化特性是由于它们能够引发类似于药物本身产生的神经事件。考虑到大量证据表明可卡因的非条件行为特性涉及中脑边缘多巴胺能投射，本研究使用体内微透析来确定与可卡因配对的刺激是否引起与该药物的非条件作用类似的中脑核中间质多巴胺的增加。产生了一个有力的无条件增加间质多巴胺浓度（基础值的300%）在脑桥核。两个独立实验的结果表明，与特定环境相关的可卡因（10 mg/kg，持续7天）给药在该环境中产生了显著的运动。与在这两种情况下接受盐水的受试者相比，在其家中笼中接受可卡因的大鼠（假条件组）在测试当天没有表现出增加的运动。虽然重复配对的可卡因与特定的环境产生的条件运动，没有伴随的条件增加多巴胺的释放。具体而言，在暴露于条件环境后观察到的多巴胺适度增加（高于基础值10-15%）在条件组和假条件组中是相等的。此外，增加多巴胺代谢产物3，4-二羟基苯乙酸和高香草酸的间质浓度的条件和pseudoconditioned subjects.These数据之间没有显着差异不支持这一假设，即刺激与可卡因配对产生其行为的影响，引起类似的神经化学作用可卡因。
The potent reinforcing effects of cocaine can readily become associated with salient environmental stimuli that acquire secondary reinforcing properties. This phenomenon is of considerable significance as intense craving can be evoked by stimuli previously associated with the effects of cocaine. It has been proposed that the reinforcing properties of these conditional stimuli are due to their ability to elicit neural events that are similar to those produced by the drug itself. Given the large body of evidence that implicates the mesolimbic dopaminergic projection in the unconditioned behavioural properties of cocaine, the present study used in vivo microdialysis to determine whether stimuli paired with cocaine elicit increases in interstitial dopamine in the nucleus accumbens that are similar to the unconditioned effects of this drug.When administered acutely, cocaine (10 mg/kg, i.p.) produced a potent unconditioned increase in interstitial dopamine concentrations (300% of basal values) in the nucleus accumbens. The results from two separate experiments indicate that the administration of cocaine (10 mg/kg for seven days) in association with a specific environment produced significant locomotion in that environment. Compared to subjects that received saline in both settings, rats that received cocaine in their home cage (pseudoconditioned group) did not exhibit increased locomotion on the test day. Although repeated pairing of cocaine with a specific environment produced conditioned locomotion, there was no concomitant conditional increase in dopamine release. Specifically, the modest increase in dopamine (10-15% above basal values) observed after exposure to the conditional environment was equal in the conditioned and pseudoconditioned groups. Moreover, increases in the interstitial concentrations of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were not significantly different between the conditioned and pseudoconditioned subjects.These data do not support the hypothesis that stimuli paired with cocaine produce their behavioural effects by eliciting similar neurochemical effects as cocaine.