Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat
Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat
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DOI：
10.1111/j.1460-9568.2006.04792.x
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Haas, H. L.
中科院分区：
文献类型：
--
作者：
Korotkova, T. M.;Brown, R. E.;Haas, H. L.
许多神经肽调节进食和唤醒；腹侧被盖区（VTA）可能是它们起作用的部位之一。我们使用全细胞膜片钳和单单元细胞外记录来检查此类神经肽对 VTA 神经元活动的影响。 P物质（SP；300 nM）增加了大多数VTA多巴胺能和γ-氨基丁酸（GABA）能神经元的放电率，并诱导两个多巴胺能细胞的振荡。促肾上腺皮质激素释放因子（CRF；200 nM）直接兴奋大多数 VTA 细胞，而神经肽 Y（NPY；300 nM）直接抑制一部分多巴胺能和 GABA 能细胞。连续应用几种神经肽表明所有神经元都被兴奋性神经肽SP、CRF或/和食欲素中的至少一种兴奋。 α-黑素细胞刺激激素对多巴胺能细胞（浓度为 500 nM 和 1 μM）没有影响，并且仅影响一小部分 GABA 能神经元。 Ghrelin (500 nM)、刺豚鼠相关肽 (1 μM)；可卡因和安非他明相关转录物（500 nM）和瘦素（500 nM和1 mu M）不调节VTA神经元的放电率和膜电位。单细胞逆转录聚合酶链反应分析表明，所有 NPY 受体均存在于 VTA 神经元中，并且除 1 个细胞外的所有细胞均表达 NPY 和/或至少一种 NPY 受体。 CRF在70%的多巴胺能VTA细胞中表达； CRF 受体 2 的表达比受体 1 的表达更丰富。这些发现表明神经肽促进觉醒的能力与其对 VTA 神经元的作用之间存在联系。
Many neuropeptides regulate feeding and arousal; the ventral tegmental area (VTA) is likely to be one site where they act. We used whole-cell patch-clamp and single-unit extracellular recordings to examine the effects of such neuropeptides on the activity of VTA neurons. Substance P (SP; 300 nM) increased the firing rate of the majority of VTA dopaminergic and gamma-aminobutyric acid (GABA)ergic neurons, and induced oscillations in two dopaminergic cells. Corticotropin-releasing factor (CRF; 200 nM) excited the majority of VTA cells directly, whereas neuropeptide Y (NPY; 300 nM) directly inhibited a subset of dopaminergic and GABAergic cells. Consecutive application of several neuropeptides revealed that all the neurons were excited by at least one of the excitatory neuropeptides SP, CRF or/and orexins. alpha-Melanocyte-stimulating hormone had no effect on dopaminergic cells (at concentrations of 500 nM and 1 mu M) and affected only a small proportion of GABAergic neurons. Ghrelin (500 nM), agouti-related peptide (1 mu M); cocaine and amphetamine-related transcript (500 nM) and leptin (500 nM and 1 mu M) did not modulate the firing rate and membrane potential of VTA neurons. Single-cell reverse transcription polymerase chain reaction analysis showed that all NPY receptors were present in VTA neurons, and all but one cell expressed NPY and/or at least one NPY receptor. CRF was expressed in 70% of dopaminergic VTA cells; the expression of CRF receptor 2 was more abundant than that of receptor 1. These findings suggest a link between the ability of neuropeptides to promote arousal and their action on VTA neurons.