Division of Bio-information Engineering, University of Toyama, 3190 Gofuku, Toyama City, Toyama 930-8555, Japan.
Peptides. 2011 Feb;32(2):246-52. doi: 10.1016/j.peptides.2010.10.023. Epub 2010 Nov 3.
Orexin (ORX) plays a critical role in reward-seeking behavior for natural rewards and drugs of abuse. The mesolimbic dopamine (DA) pathway that projects into the nucleus accumbens (NAc) from the ventral tegmental area is deeply involved in the neural mechanisms underlying reward, drug abuse and motivation. A recent study demonstrated that ORX-immunopositive fibers densely project into the shell of the NAc (NAcSh), suggesting that the NAcSh might be a site of the interaction between the ORXergic and DAergic systems for reward-seeking behavior. Therefore, the electrophysiological effects of ORX-B and DA on NAcSh neurons were examined extracellularly in rat brain slice preparations. ORX-B excited approximately 78% of neurons tested and inhibited 4%, whereas DA excited 50% and inhibited 22% of NAcSh neurons. These excitations and inhibitions persisted during synaptic blockade in a low-Ca(2+)/high-Mg(2+) solution. DA-induced excitation was attenuated by SCH23390 or sulpiride, whereas DA-induced inhibition was suppressed by sulpiride. Of the neurons that were excited by ORX-B, 71% and 18% were excited and inhibited by DA, respectively. In 63% of neurons that were excited by ORX-B, the simultaneous application of ORX-B and DA increased the firing rate to two times greater than ORX-B alone, whereas, the simultaneous application significantly decreased the neuronal firing rate by 73% in the remaining 37% compared to ORX-B. These results suggest that an interaction between the ORXergic and DAergic systems occurs in the NAcSh and that the NAcSh is involved in the neural mechanisms in which ORX participates in the regulation of reward-seeking behavior.
食欲素（ORX）在天然奖赏和滥用药物的觅药行为中起着关键作用。从中脑腹侧被盖区（VTA）投射到伏隔核（NAc）的中脑边缘多巴胺（DA）通路，深入参与了奖赏、药物滥用和动机的神经机制。最近的一项研究表明，ORX 免疫阳性纤维密集投射到 NAc 的壳（NAcSh），这表明 NAcSh 可能是 ORX 能系统和 DA 能系统参与觅药行为相互作用的部位。因此，在大鼠脑切片制备中，体外研究了 ORX-B 和 DA 对 NAcSh 神经元的电生理效应。ORX-B 兴奋了约 78%的测试神经元，并抑制了 4%，而 DA 兴奋了 50%，抑制了 22%的 NAcSh 神经元。在低钙（Ca2+）/高镁（Mg2+）溶液中，这些兴奋和抑制在突触阻断时仍然存在。SCH23390 或 sulpiride 减弱了 DA 诱导的兴奋，而 sulpiride 抑制了 DA 诱导的抑制。在被 ORX-B 兴奋的神经元中，71%和 18%分别被 DA 兴奋和抑制。在 63%的被 ORX-B 兴奋的神经元中，ORX-B 和 DA 的同时应用将放电率提高到两倍于 ORX-B 单独应用的水平，而在其余 37%的神经元中，与 ORX-B 相比，同时应用显著降低了神经元放电率 73%。这些结果表明，ORX 能系统和 DA 能系统在 NAcSh 中相互作用，并且 NAcSh 参与了 ORX 参与调节觅药行为的神经机制。
