Heinrichs S.C., Menzaghi F., Schulteis G., Koob G.F., Stinus L.
Department of Neuropharmacology CVN7, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
Behav Pharmacol. 1995 Jan;6(1):74-80.
The central nucleus of the amygdala is a CRF-containing limbic brain site which mediates both fear-like and avoidance behaviors, and intra-amygdala administration of a CRF antagonist blocks the increase in anxiogenic-like behavior characteristic of ethanol withdrawal. In order to evaluate the role of brain CRF in negative motivational states associated with other classes of abused drugs, the present studies examined the effects of suppression of amygdala CRF systems on the characteristic aversive state of precipitated withdrawal in morphine-dependent subjects. In a place conditioning paradigm, administration of a CRF antagonist, alpha-belical CRF (9-41) [250ng], bilaterally into the central nucleus of amygdala, reversed the withdrawal-induced conditioned place aversion produced by injection of the opiate antagonist, methylnaloxonium [500ng], into the same site. In a conditioned operant suppression paradigm, impairment of CRF neurons by immuno-targeted toxins administered into the central nucleus of amygdala, one month prior to testing, attenuated the decrease in response rate produced by exposure to distinctive sensory cues associated previously with systemic administration of naloxone [25µg/kg s.c.] in morphine-dependent subjects. These results indicate that suppression of intra-amygdala CRF systems weakens the aversive stimulus properties of conditioned opiate withdrawal, and suggest a general role for CRF in coordinating behavioral responses to negative motivational effects of drug withdrawal.
杏仁核中央核是一个含有促肾上腺皮质激素释放因子（CRF）的边缘脑区，它介导恐惧样行为和回避行为，向杏仁核内注射CRF拮抗剂可阻断乙醇戒断时出现的焦虑样行为增加。为了评估脑内CRF在与其他类滥用药物相关的负性动机状态中的作用，本研究检测了抑制杏仁核CRF系统对吗啡依赖受试者戒断诱发的特征性厌恶状态的影响。在位置条件反射范式中，向杏仁核中央核双侧注射CRF拮抗剂α-螺旋CRF（9-41）[250ng]，可逆转由向同一部位注射阿片拮抗剂甲基纳洛酮[500ng]所产生的戒断诱导的条件性位置厌恶。在条件性操作式抑制范式中，在测试前一个月向杏仁核中央核注射免疫靶向毒素损害CRF神经元，可减弱吗啡依赖受试者暴露于先前与皮下注射纳洛酮[25µg/kg]全身给药相关的独特感觉线索时所产生的反应率下降。这些结果表明，抑制杏仁核内CRF系统可减弱条件性阿片戒断的厌恶刺激特性，并提示CRF在协调对药物戒断负性动机效应的行为反应中具有普遍作用。
