Geary W A, Wooten G F
Brain Res. 1985 Apr 15;332(1):69-78. doi: 10.1016/0006-8993(85)90390-7.
We have simultaneously studied regional cerebral glucose utilization (RCGU) and behavior during naloxone precipitated morphine withdrawal. For RCGU studies, 25 brain regions were analyzed that previously had been shown to participate in morphine withdrawal. Four established behavioral signs of morphine withdrawal were recorded: wet shakes, jumping, weight loss, and autonomic signs. Using a 10(4) range of naloxone dose (0.0005-5.0 mg/kg), dose dependent effects were found for 3 behaviors: jumping, weight loss and autonomic signs. The incidence of wet shakes did not correlate with naloxone dose. Increases in RCGU in several specific brain sites were also naloxone dose dependent. Naloxone dose dependent increases in RCGU during precipitated morphine withdrawal may be divided into 3 classes of responses: Class I structures (paraventricular, ventromedial, and lateral hypothalamus) exhibited their largest RCGU increases between 0.005 and 0.05 mg/kg of naloxone; Class II structures (preoptic areas, basal ganglia, anterior and intralaminar thalamic nuclei, mammillary nuclei, and certain midbrain regions) showed gradual RCGU increases across the 10(4) range of naloxone dose; and, Class III structures (diagonal band, medial and lateral septum, and the central amygdaloid nucleus) displayed large RCGU increases across 0.5-5.0 mg/kg of naloxone. Regression analysis of RCGU vs behavior showed correlations between Class I responses and autonomic signs (P less than 0.010); weight loss was correlated with all 3 classes of naloxone dose dependent RCGU responses during withdrawal (P less than 0.05). The strong positive correlation among these RCGU increases and certain morphine withdrawal behaviors supported the use of RCGU measurements in specific brain sites as a sensitive and objective biochemical indicator of the presence and severity of morphine dependence. In addition, this study demonstrates that changes in RCGU in different brain regions are heterogeneous with respect to naloxone dose and appear reproducibly along a continuum from mild to severe withdrawal.
我们同时研究了纳洛酮诱发吗啡戒断期间的局部脑葡萄糖利用（RCGU）和行为。对于RCGU研究，分析了先前已显示参与吗啡戒断的25个脑区。记录了吗啡戒断的四种既定行为体征：湿抖、跳跃、体重减轻和自主神经体征。使用10⁴范围的纳洛酮剂量（0.0005 - 5.0 mg/kg），发现3种行为存在剂量依赖性效应：跳跃、体重减轻和自主神经体征。湿抖的发生率与纳洛酮剂量无关。几个特定脑区的RCGU增加也呈纳洛酮剂量依赖性。纳洛酮诱发吗啡戒断期间RCGU的剂量依赖性增加可分为3类反应：I类结构（室旁核、腹内侧核和外侧下丘脑）在纳洛酮0.005至0.05 mg/kg之间表现出最大的RCGU增加；II类结构（视前区、基底神经节、丘脑前核和板内核、乳头体核以及某些中脑区域）在纳洛酮10⁴剂量范围内显示RCGU逐渐增加；III类结构（斜角带、内侧和外侧隔区以及中央杏仁核）在纳洛酮0.5至5.0 mg/kg之间显示出较大的RCGU增加。RCGU与行为的回归分析显示I类反应与自主神经体征之间存在相关性（P小于0.010）；体重减轻与戒断期间所有3类纳洛酮剂量依赖性RCGU反应相关（P小于0.05）。这些RCGU增加与某些吗啡戒断行为之间的强正相关支持了在特定脑区进行RCGU测量，作为吗啡依赖存在和严重程度的敏感且客观的生化指标。此外，本研究表明，不同脑区的RCGU变化在纳洛酮剂量方面是异质性的，并且从轻度到重度戒断沿连续体可重复出现。
