Sarnyai Z, Bíró E, Gardi J, Vecsernyés M, Julesz J, Telegdy G
Department of Pathophysiology, Albert Szent Györgyi Medical University, Szeged, Hungary.
Brain Res. 1995 Mar 27;675(1-2):89-97. doi: 10.1016/0006-8993(95)00043-p.
Anxiety is a key symptom of the cocaine withdrawal syndrome in human addicts, and it is considered to be one of the major factors in precipitating relapse to chronic cocaine abuse. Corticotropin-releasing factor (CRF) plays an important role in the pathophysiology of anxiety and depression, and it may also be involved in the acute behavioral and neuroendocrine actions of cocaine. The role of endogenous CRF in cocaine withdrawal-induced anxiety was investigated in the present study. Animals were subjected to chronic cocaine (20 mg/kg, intraperitoneally, once a day for 14 days) administration. Rats tested 30 min after the last cocaine injection did not show withdrawal anxiety on the elevated plus maze or any alterations in brain CRF levels. Withdrawal (48 h) from chronic cocaine administration produced an intense anxiety-like behavior characterized by decreased open arm exploration. Immunoreactive CRF (CRF-LI) levels were selectively altered in the hypothalamus, in the amygdala and in the basal forebrain structures at the time of the behavioral anxiety, reflecting an increased activity of brain CRF systems. Daily intracerebroventricular (i.c.v.) pretreatment with an immunoserum raised against CRF completely prevented the development of anxiety induced by cocaine withdrawal. These data suggest that extrahypothalamic-limbic CRF hypersecretion may be involved in the development of anxiety related to cocaine withdrawal and that the CRF system may be a useful target for new pharmacotherapies for cocaine withdrawal and relapse.
焦虑是人类可卡因成瘾者戒断综合征的关键症状，并且被认为是促使复吸慢性可卡因滥用的主要因素之一。促肾上腺皮质激素释放因子（CRF）在焦虑和抑郁的病理生理学中起重要作用，并且它也可能参与可卡因的急性行为和神经内分泌作用。本研究调查了内源性CRF在可卡因戒断所致焦虑中的作用。对动物进行慢性可卡因（20mg/kg，腹腔注射，每天一次，共14天）给药。在最后一次注射可卡因后30分钟进行测试的大鼠在高架十字迷宫中未表现出戒断焦虑，脑CRF水平也无任何改变。慢性可卡因给药后的戒断（48小时）产生了以开放臂探索减少为特征的强烈焦虑样行为。在行为焦虑发生时，下丘脑、杏仁核和基底前脑结构中的免疫反应性CRF（CRF-LI）水平发生了选择性改变，反映出脑CRF系统的活性增加。每天经脑室内（i.c.v.）用针对CRF产生的免疫血清进行预处理可完全预防可卡因戒断所致焦虑的发生。这些数据表明，下丘脑外边缘系统CRF分泌过多可能参与了与可卡因戒断相关的焦虑的发生，并且CRF系统可能是可卡因戒断和复吸新药物治疗的有用靶点。
