Kraus M A, Piper J M, Kornetsky C
Department of Pharmacology, Boston University School of Medicine, MA 02118, USA.
Brain Res. 1996 Jun 10;724(1):33-40. doi: 10.1016/0006-8993(96)00263-6.
The current 2-deoxy-D-[1-14C]glucose investigation was performed to test the hypothesis that endogenous opioids influence basal synaptic activity within discrete brain regions. To examine this hypothesis, the effects of naloxone (1.0 mg/kg s.c.) on local cerebral metabolic rate for glucose (LCMRglu) in 84 brain regions were compared to saline controls. The specificity of naloxone's effects for opioid receptors was assessed by the coadministration of the opiate agonist morphine in a separate group. In naloxone-treated rats, there was a significant decrease in LCMRglu in the locus coeruleus (LC) and an increase in the central nucleus of the amygdala (CAMY), supporting a tonic influence of endogenous opioids on these regions. These metabolic changes were reversed by coadministered morphine, indicating that naloxone's metabolic actions are specific for opioid receptors. Based on the role of the LC and CAMY in opiate withdrawal, the present results suggest a subthreshold naloxone precipitated withdrawal from endogenous opioids. Although morphine administered alone significantly reduced LCMRglu in 16 brain regions, these did not include the LC or the CAMY. These results identify brain regions in which synaptic activity is under tonic modulation by endogenous opioids.
当前进行的2-脱氧-D-[1-14C]葡萄糖研究旨在检验内源性阿片类物质影响离散脑区内基础突触活动这一假说。为检验该假说，将纳洛酮（1.0毫克/千克，皮下注射）对84个脑区局部脑葡萄糖代谢率（LCMRglu）的影响与生理盐水对照组进行了比较。在另一组中通过同时给予阿片类激动剂吗啡来评估纳洛酮作用于阿片受体的特异性。在接受纳洛酮治疗的大鼠中，蓝斑（LC）的LCMRglu显著降低，杏仁核中央核（CAMY）的LCMRglu升高，这支持了内源性阿片类物质对这些区域的紧张性影响。同时给予吗啡可逆转这些代谢变化，表明纳洛酮的代谢作用对阿片受体具有特异性。基于LC和CAMY在阿片类物质戒断中的作用，目前的结果提示亚阈值剂量的纳洛酮引发了内源性阿片类物质的戒断反应。尽管单独给予吗啡可显著降低16个脑区的LCMRglu，但这些脑区不包括LC或CAMY。这些结果确定了突触活动受内源性阿片类物质紧张性调节的脑区。
