Yin Henry H, Adermark Louise, Lovinger David M
NIAAA/NIH, Bethesda, MD 20892, USA.
Neuropharmacology. 2008 Jan;54(1):79-86. doi: 10.1016/j.neuropharm.2007.06.004. Epub 2007 Jun 22.
Neurotensin is a peptide that has been suggested to mimic the actions of antipsychotics, but little is known about how it affects synaptic transmission in the striatum, the major input nucleus of the basal ganglia. In this study we measured the effects of neurotensin on EPSCs from medium spiny projection neurons in the sensorimotor striatum, a region implicated in habit formation and control of motor sequences. We found that bath-applied neurotensin reduced glutamate release from presynaptic terminals, and that this effect required retrograde endocannabinoid signaling, as it was prevented by the CB1 cannabinoid receptor antagonist AM251. Neurotensin-mediated inhibition of striatal EPSCs was also blocked by antagonists of D2-like dopamine receptors and group I metabotropic glutamate receptors, as well as by intracellular calcium chelation and phospholipase C inhibition. These results suggest that neurotensin can indirectly engage an endocannabinoid-mediated negative feedback signal to control glutamatergic input to the basal ganglia.
神经降压素是一种被认为可模拟抗精神病药物作用的肽，但对于它如何影响纹状体（基底神经节的主要输入核团）中的突触传递，人们知之甚少。在本研究中，我们测量了神经降压素对感觉运动纹状体中中等棘状投射神经元的兴奋性突触后电流（EPSCs）的影响，该区域与习惯形成和运动序列控制有关。我们发现，浴加神经降压素可减少突触前终末的谷氨酸释放，且这种作用需要逆行性内源性大麻素信号传导，因为CB1大麻素受体拮抗剂AM251可阻止此效应。神经降压素介导的纹状体EPSCs抑制作用也被D2样多巴胺受体拮抗剂、I组代谢型谷氨酸受体拮抗剂以及细胞内钙螯合剂和磷脂酶C抑制剂所阻断。这些结果表明，神经降压素可间接激活内源性大麻素介导的负反馈信号，以控制基底神经节的谷氨酸能输入。
