Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs
Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs
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DOI：
10.1016/j.neubiorev.2003.11.001
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发表时间：
2004-01-01
影响因子：
8.2
通讯作者：
Vezina, P
中科院分区：
文献类型：
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作者：
Vezina, P
像安非他明这样的精神兴奋剂药物很容易被人类和实验室动物自行服用，因为它们对中脑的多巴胺（DA）神经元起作用。将动物全身或腹侧被盖区这些神经元的细胞体区域暴露于该药物导致多巴胺能功能的长期改变。这些最常被评估为在数周至数月后再次暴露于药物后增加的运动活性和增强的延髓核（NAcc）中的DA溢出。有证据表明，产生这种致敏的中脑DA神经元反应的操作，提高了精神兴奋剂药物的追求和自我管理。已知的防止安非他明诱发致敏的程序也防止了吸毒的便利化。增强的药物自我给药和药物寻求的启动恢复也伴随着增强的NAcc DA反应性。最后，药物增加NAcc DA溢出急性，但未能产生这种效应的敏化与随后的自我管理的增强。这些结果表明，中脑多巴胺神经元反应性的敏化和过度追求和自我管理的精神兴奋剂药物之间的直接关系。因此，了解神经元的事件和适应性的诱导和表达的敏化可能有助于阐明药物滥用的发展，它是如何恢复，并最终如何两者都可以防止。(C)2003爱思唯尔有限公司。保留所有权利。
Psychostimulant drugs like amphetamine are readily self-administered by humans and laboratory animals by virtue of their actions on dopamine (DA) neurons in the midbrain. Exposing animals to this drug either systemically or in the cell body region of these neurons in the ventral tegmental area leads to long-lasting alterations in dopaminergic function. These have most often been assessed as increased locomotor activity and enhanced DA overflow in the nucleus accumbens (NAcc) after re-exposure to the drug weeks to months later. Evidence is presented showing that manipulations that produce this sensitization of midbrain DA neuron reactivity enhance the pursuit and self-administration of psychostimulant drugs. Procedures known to prevent the induction of sensitization by amphetamine also prevent the facilitation of drug taking. Enhanced drug self-administration and primed reinstatement of drug seeking are also accompanied by enhanced NAcc DA reactivity. Finally, drugs that increase NAcc DA overflow acutely but fail to produce sensitization of this effect are not associated with the subsequent enhancement of self-administration. These results indicate a direct relationship between the sensitization of midbrain dopamine neuron reactivity and the excessive pursuit and self-administration of psychostimulant drugs. Understanding the neuronal events and adaptations that underlie the induction and expression of sensitization may thus help elucidate how drug abuse develops, how it is reinstated and ultimately how both may be prevented. (C) 2003 Elsevier Ltd. All rights reserved.