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重新评估吗啡对猫的作用:III. 完整动物、尾状核损伤动物及大脑半球切除动物在长期给药及诱发戒断后的反应

Reassessing morphine effects in cats: III. Responses of intact, caudate nuclei-lesioned and hemispherectomized animals following chronic administration and precipitated withdrawal.

作者信息

Harris C M, Villablanca J R, Burgess J W, de Andres I

出版信息

Pharmacol Biochem Behav. 1984 Dec;21(6):929-36. doi: 10.1016/s0091-3057(84)80075-1.

Abstract

Behavioral response to low doses of morphine (2.0 to 3.0 mg/kg, IP) administered for up to 15 days, and responses to subsequent naloxone challenges, were measured in intact, unilaterally and bilaterally caudate-lesioned (acaudate) cats, and in hemispherectomized cats using a video time-sampling method. For all groups minor tolerance to posture and movement activation patterns was seen, with a reciprocal increase in motor relaxation, which was somewhat more marked for acaudate cats. In contrast to this weak tolerance, all cats showed strong, typical withdrawal manifestations at the beginning of abstinence and a "mini withdrawal" could still be precipitated 15-30 days later when morphine was no longer detectable in the blood. The cats with the unilateral lesions showed whole body turning toward the lesioned side after morphine and away from the lesioned side following naloxone. Only hemispherectomized and acaudate animals showed significant physical deterioration (e.g., weight loss, decreased activity). The comparisons between weak tolerance development versus strong physical dependence and the possible mechanisms involved in shifting the turning biases are discussed. The potential of the cat as a model for studying opiate effects is stressed.

摘要

采用视频时间采样法,对完整、单侧和双侧尾状核损伤(无尾状核)的猫以及大脑半球切除的猫,测量其对连续15天给予低剂量吗啡(2.0至3.0毫克/千克,腹腔注射)的行为反应,以及随后对纳洛酮激发试验的反应。所有组对姿势和运动激活模式均出现轻微耐受性,同时运动放松程度相应增加,这在无尾状核的猫中更为明显。与这种微弱耐受性相反,所有猫在戒断开始时均表现出强烈、典型的戒断表现,并且在15 - 30天后,当血液中不再检测到吗啡时,仍可引发“轻微戒断”。单侧损伤的猫在注射吗啡后全身转向损伤侧,注射纳洛酮后则远离损伤侧。只有大脑半球切除的动物和无尾状核的动物出现明显的身体恶化(如体重减轻、活动减少)。文中讨论了微弱耐受性发展与强烈身体依赖性之间的比较,以及改变转向偏向可能涉及的机制。强调了猫作为研究阿片类药物作用模型的潜力。

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