Opioids excite dopamine neurons by hyperpolarization of local interneurons
Opioids excite dopamine neurons by hyperpolarization of local interneurons
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DOI：
10.1523/jneurosci.12-02-00483.1992
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发表时间：
1992-02
期刊：
影响因子：
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通讯作者：
S. Johnson;R. North
中科院分区：
文献类型：
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作者：
S. Johnson;R. North
腹侧被盖区含多巴胺神经元的活性增加对于阿片类药物和其他滥用药物的强化作用是必要的。体外大鼠脑切片中这些细胞的细胞内记录表明，阿片类药物不影响主要（含多巴胺）神经元，但影响高兴奋性次级（含GABA）中间神经元。对阿片受体亚型具有选择性的激动剂和拮抗剂的实验表明，次级细胞的超极化涉及μ受体。大多数主细胞表现出自发荷包牡丹碱敏感的突触电位时，细胞外钾浓度从2.5增加到6.5或10.5 mM;这些被TTX阻止，并假设导致轻微去极化的本地interneurons产生的动作电位。这些突触电位的频率，但不是他们的振幅，减少阿片类药物选择性μ受体。它的结论是，超极化的中间神经元阿片类药物减少自发GABA介导的突触输入多巴胺细胞。在体内，这将导致多巴胺细胞通过去抑制而兴奋，这将被预期有助于用μ受体激动剂如吗啡和海洛因所看到的正强化。
Increased activity of dopamine-containing neurons in the ventral tegmental area is necessary for the reinforcing effects of opioids and other abused drugs. Intracellular recordings from these cells in slices of rat brain in vitro showed that opioids do not affect the principal (dopamine-containing) neurons but hyperpolarize secondary (GABA- containing) interneurons. Experiments with agonists and antagonists selective for opioid receptor subtypes indicated that the hyperpolarization of secondary cells involved the mu-receptor. Most principal cells showed spontaneous bicuculline-sensitive synaptic potentials when the extracellular potassium concentration was increased from 2.5 to 6.5 or 10.5 mM; these were prevented by TTX and assumed to result from action potentials arising in slightly depolarized local interneurons. The frequency of these synaptic potentials, but not their amplitudes, was reduced by opioids selective for mu-receptors. It is concluded that hyperpolarization of the interneurons by opioids reduces the spontaneous GABA-mediated synaptic input to the dopamine cells. In vivo, this would lead to excitation of the dopamine cells by disinhibition, which would be expected to contribute to the positive reinforcement seen with mu-receptor agonists such as morphine and heroin.