Electrophysiological and pharmacological characteristics of nigral dopaminergic neurons in the conscious, head-restrained rat
Electrophysiological and pharmacological characteristics of nigral dopaminergic neurons in the conscious, head-restrained rat
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DOI：
10.1002/syn.10177
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发表时间：
2003-04-01
期刊：
影响因子：
2.3
通讯作者：
Gessa, GL
中科院分区：
文献类型：
--
作者：
Fà, M;Mereu, G;Gessa, GL
我们从有意识的大鼠身上获得了黑质多巴胺（DA）神经元的细胞外单单元记录，这些大鼠习惯于将身体悬挂在布衣中，并通过永久固定在头骨上的“抑制平台”将头部固定在立体定向框架中。将头部受限大鼠DA神经元的电生理特征及其对阿波吗啡和氟哌啶醇的反应与水合氯醛轻、深麻醉大鼠和中脑切片的单单元记录进行比较。与轻度和深度麻醉大鼠相比，头部限制大鼠自发性活动的DA神经元数量和破裂神经元百分比更高。事实上，在深度麻醉的大鼠中，爆发活动是罕见的，在切片中完全没有。氟哌啶醇对头部约束大鼠的放电率和爆发活动的刺激作用比轻度麻醉大鼠更有效，而对深度麻醉大鼠几乎无效，对切片完全无效。另一方面，头部受限大鼠的DA神经元显示出与轻度和深度麻醉大鼠以及切片相同的平均放电率。阿波啡抑制放电速率的效力和氟哌啶醇逆转阿波啡作用的效力在不同体内制剂中没有差异。结果表明，水合氯醛麻醉不仅会减弱或抑制通常维持自发活跃的DA神经元数量及其爆发活动的兴奋性输入，还会减弱氟哌啶醇诱导的D-2受体阻断后DA神经元的反馈兴奋。另一方面，水合氯醛麻醉既不改变D-2自身受体对阿扑吗啡和氟哌啶醇的敏感性，也不改变动作电位的自动产生。头部受限大鼠似乎是研究DA神经元药理学和生理学的重要模型。
Extracellular single-unit recordings of nigral dopamine (DA) neurons were obtained from conscious rats habituated to having their body suspended in a cloth jacket and their head immobilized in the stereotaxic frame by means of a "restraining platform" permanently fixed to the skull. The electrophysiological characteristics of DA neurons from head-restrained rats and their responses to apomorphine and haloperidol were compared with single-unit recordings obtained from rats lightly and deeply anesthetized with chloral hydrate and from mesencephalic slices. Head-restrained rats showed a higher number of spontaneously active DA neurons and a higher percentage of bursting neurons than lightly and deeply anesthetized rats. Indeed, bursting activity was rare in deeply anesthetized rats and was totally absent in slices. Haloperidol was more potent and effective in stimulating the firing rate and bursting activity in head-restrained than in lightly anesthetized rats, while it was virtually ineffective in deeply anesthetized rats and totally ineffective in slices. On the other hand, DA neurons in head-restrained rats showed the same average firing rate as DA neurons in lightly and deeply anesthetized rats and in slices. The potency of apomorphine in inhibiting the firing rate, and that of haloperidol in reversing apomorphine effect, did not vary among the different in vivo preparations. The results suggest that chloral hydrate anesthesia blunts or suppresses not only the excitatory inputs which normally sustain the number of spontaneously active DA neurons and their bursting activity, but also the feedback excitation of DA neurons following haloperidol-induced D-2 receptor blockade. On the other hand, chloral hydrate anesthesia modifies neither D-2 autoreceptor sensitivity to apomorphine and haloperidol nor the automatic genesis of action potentials. The head-restrained rat appears to be an important model for studies into the pharmacology and physiology of DA neurons.