Murphy N P, Maidment N T
Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, UCLA School of Medicine, Los Angeles, California 90024-1759, USA.
J Neurochem. 1999 Jul;73(1):179-86. doi: 10.1046/j.1471-4159.1999.0730179.x.
Orphanin FQ has been reported to suppress extracellular dopamine levels in the nucleus accumbens after intracerebroventricular administration. This study sought to provide evidence for an intra-ventral tegmental site of action for this effect using a dual-probe microdialysis experimental design. Orphanin FQ was applied to the ventral tegmental area of anesthetized rats by reverse dialysis while extracellular dopamine was sampled with a second dialysis probe in the nucleus accumbens. Orphanin FQ at a probe concentration of 1 mM (but not at 0.1 mM) significantly reduced nucleus accumbens dialysate dopamine levels. The receptor-inactive analogue, des-Phe1-orphanin FQ (1 mM), produced a small but significant increase in nucleus accumbens dialysate dopamine levels. Simultaneous measurement of ventral tegmental area dialysate amino acid content revealed significant increases in both GABA and glutamate during infusion of orphanin FQ (1 mM). To determine if increased GABA overflow mediates the action of orphanin FQ on mesolimbic neurons, orphanin FQ (10 nmol) was microinjected directly into the ventral tegmental area in the presence or absence of the GABA(A) receptor antagonist, bicuculline (1 nmol). Bicuculline transiently blocked the suppressive action of orphanin FQ on accumbens dialysate dopamine levels. These data indicate that orphanin FQ decreases dopamine transmission in the nucleus accumbens by inhibiting dopamine neuronal activity in the ventral tegmental area through a mechanism that may involve an increased overflow of GABA.
据报道，脑室内注射孤啡肽后可抑制伏隔核细胞外多巴胺水平。本研究旨在通过双探针微透析实验设计，为孤啡肽这一作用的腹侧被盖区作用位点提供证据。通过反向透析将孤啡肽应用于麻醉大鼠的腹侧被盖区，同时用第二个透析探针在伏隔核采集细胞外多巴胺样本。探针浓度为1 mM的孤啡肽（而非0.1 mM）显著降低了伏隔核透析液中的多巴胺水平。受体失活类似物去苯丙氨酸1 - 孤啡肽（1 mM）使伏隔核透析液中的多巴胺水平出现了虽小但显著的升高。同时测量腹侧被盖区透析液中的氨基酸含量发现，在注入孤啡肽（1 mM）期间，GABA和谷氨酸含量均显著增加。为了确定GABA溢出增加是否介导了孤啡肽对中脑边缘神经元的作用，在存在或不存在GABA(A)受体拮抗剂荷包牡丹碱（1 nmol）的情况下，将孤啡肽（10 nmol）直接微量注射到腹侧被盖区。荷包牡丹碱短暂阻断了孤啡肽对伏隔核透析液多巴胺水平的抑制作用。这些数据表明，孤啡肽通过一种可能涉及GABA溢出增加的机制，抑制腹侧被盖区多巴胺神经元活动，从而降低伏隔核中的多巴胺传递。
