Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms.
Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms.
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DOI：
10.1016/j.ejphar.2015.07.044
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发表时间：
2015-10-05
影响因子：
5
通讯作者：
Shi WX
中科院分区：
文献类型：
--
作者：
Dela Peña I;Gevorkiana R;Shi WX
可卡因和苯丙胺类精神兴奋剂发挥其强化作用的确切机制尚未完全确定。然而，人们普遍认为，这些药物通过诱导多巴胺转运蛋白介导的反向转运和/或通过多巴胺转运蛋白阻断多巴胺再摄取来增强大脑中的多巴胺神经传递，特别是在边缘系统区域如丘脑核中。在这里，我们提出的证据表明，除了多巴胺转运蛋白，非多巴胺转运蛋白介导的机制也参与了精神兴奋剂诱导的多巴胺释放，并有助于这些药物的行为效应，如自发激活和奖励。因此，精神兴奋剂可以增加前额叶皮层中的去甲肾上腺素释放，后者然后改变多巴胺神经元的放电模式，导致动作电位依赖性多巴胺释放的变化。这些改变将进一步影响中脑背外侧核多巴胺释放的时间模式，从而改变该区域的信息处理。因此，多巴胺可以增强或抑制突触输入到脑桥核神经元，这取决于其与多巴胺释放的时间关系。多巴胺释放的特定时间模式也可能是脑桥核中某些形式的突触可塑性所必需的。总之，由精神兴奋剂诱导的这些效应，通过涉及去甲肾上腺素和前额叶皮层的非多巴胺转运蛋白介导的机制介导，也可能对这些药物的强化特性做出重要贡献。
The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs.