Stinus L, Le Moal M, Koob G F
Psychobiologies des Comportements Adaptatifs, INSERM, Unité 259, Bordeaux, France.
Neuroscience. 1990;37(3):767-73. doi: 10.1016/0306-4522(90)90106-e.
Specific brain sites for the opiate abstinence syndrome syndrome have been elusive to delineate, and the classic overt signs of withdrawal such as wet dog shakes, ptosis and teeth chattering appear to be widely represented in the brain. Using a more general motivational test involving a disruption of operant behavior in dependent rats, the brain site most sensitive to the response disruptive effects of intracerebral administration of the opiate antagonist, methylnaloxonium, was the region of the nucleus accumbens, a site also implicated in the acute reinforcing properties of opiates. This disruption of operant responding was hypothesized to reflect the aversive properties of opiate withdrawal. The present study directly tested that hypothesis by exploring whether intercerebral administration of methylnaloxonium produced aversive stimulus effects as measured by the formation of place aversions. Rats implanted intracerebroventricularly or with bilateral cannulae aimed at the medial dorsal thalamus, periaqueductal gray, ventral tegmental area, amygdala or nucleus accumbens were made dependent on morphine by subcutaneous implantation of two 75-mg morphine pellets. The animals were then subjected to place aversion training by pairing of a distinct environment (one of three arms of a three-armed box with distinct texture, markings and smell) with a single injection of methylnaloxonium intracerebroventricularly or intracerebrally. Results showed that at high doses of methylnaloxonium (1000-2000 ng) all sites produced a place aversion. However, lower doses (250-500 ng) produced a significant brain site selectivity with the region of the nucleus accumbens the most sensitive. Observational measurements taken during the postinjection period with the high dose of methylnaloxonium showed that agitation was particularly observed following methylnaloxonium administration into the nucleus accumbens and periaqueductal gray.(ABSTRACT TRUNCATED AT 250 WORDS)
鸦片戒断综合征在大脑中的具体位点一直难以明确界定，而诸如湿狗样抖动、上睑下垂和牙齿打颤等经典的明显戒断体征似乎在大脑中广泛存在。通过一项更具普遍性的动机测试，即干扰依赖大鼠的操作性行为，对大脑内注射鸦片拮抗剂甲基纳洛酮的反应干扰作用最敏感的脑区是伏隔核区域，该区域也与鸦片的急性强化特性有关。这种对操作性反应的干扰被认为反映了鸦片戒断的厌恶特性。本研究通过探究脑内注射甲基纳洛酮是否会产生如通过位置厌恶形成所测量的厌恶刺激效应，直接对该假设进行了测试。通过皮下植入两颗75毫克的吗啡丸使脑室内植入或双侧套管植入靶向内侧背侧丘脑、导水管周围灰质、腹侧被盖区、杏仁核或伏隔核的大鼠对吗啡产生依赖。然后，通过将一个独特的环境（一个有独特质地、标记和气味的三臂箱中的三个臂之一）与单次脑室内或脑内注射甲基纳洛酮配对，对动物进行位置厌恶训练。结果表明，在高剂量的甲基纳洛酮（1000 - 2000纳克）下，所有位点都产生了位置厌恶。然而，较低剂量（250 - 500纳克）产生了显著的脑区选择性，伏隔核区域最为敏感。在高剂量甲基纳洛酮注射后的观察测量表明，在向伏隔核和导水管周围灰质注射甲基纳洛酮后尤其观察到了躁动。（摘要截取自250字）
