Opiate tolerance by heroin self-administration: an fMRI study in rat.
Opiate tolerance by heroin self-administration: an fMRI study in rat.
复制标题
海洛因自我给药的阿片耐受性：大鼠的功能磁共振成像研究。
DOI：
10.1002/mrm.20119
复制
发表时间：
2004
影响因子：
3.3
通讯作者：
Li,Shi-Jiang
中科院分区：
文献类型：
--
作者：
Xi,Zheng-Xiong;Wu,Gaohong;Stein,ElliotA;Li,Shi-Jiang
采用功能性 MRI (fMRI) 来确定重复海洛因自我给药 (SA) 是否会在海洛因 SA 大鼠的大脑中产生耐受性或致敏性。将 12 只大鼠均匀分为盐水组和海洛因（0.06 毫克/千克，4 小时/天）SA 组。在 8-9 天的海洛因-SA 训练期间，药物-SA 行为和每日海洛因摄入量逐渐增加。在最后一次每日 SA 后 24 小时内，急性海洛因（0.1 mg/kg）给药在两组大鼠中诱导局部血氧水平依赖性（BOLD）信号。正BOLD信号主要出现在皮质区域，包括前额皮质、扣带皮层和嗅觉皮质，而负BOLD信号主要出现在皮质下区域，如尾状核和壳核、伏核、丘脑和下丘脑。然而，与生理盐水对照大鼠相比，海洛因-SA大鼠前额皮质、伏核和丘脑等区域的激活体素数量或BOLD信号强度显着减少。应用γ-乙烯基GABA（100 mg/kg）（一种不可逆的GABA转氨酶抑制剂）未能阻断海洛因-SA大鼠中的阿片类药物作用。总之，这些数据表明，重复的海洛因-SA 会在大鼠大脑中产生阿片类药物作用的耐受性或脱敏作用，这反过来可能会增强药物 SA 行为和药物摄入。 Magn Reson Med 52:108–114, 2004。© 2004 Wiley-Liss, Inc.
Functional MRI (fMRI) was employed to determine whether repeated heroin self‐administration (SA) produces tolerance or sensitization in the brain of heroin‐SA rats. Twelve rats were evenly divided into saline and heroin (0.06 mg/kg, 4 hr/day) SA groups. There was a progressive increase in drug‐SA behavior and daily heroin intake during the 8–9 days of heroin‐SA training. Within 24 hr after the last session of daily SA, acute heroin (0.1 mg/kg) administration induced regional blood oxygen level‐dependent (BOLD) signals in both groups of rats. The positive BOLD signals appeared mainly in the cortical regions, including the prefrontal cortex, cingulate, and olfactory cortex, while the negative BOLD signals were predominantly located in subcortical regions such as caudate and putamen, nucleus accumbens, thalamus, and hypothalamus. However, the number of activated voxels or BOLD‐signal intensity was significantly less in heroin‐SA rat in regions of prefrontal cortex, nucleus accumbens, and thalamus, etc., compared to the changes in the saline control rats. Application of γ‐vinyl GABA (100 mg/kg), an irreversible GABA‐transaminase inhibitor, failed to block opiate actions in the heroin‐SA rats. Together, these data suggest that repeated heroin‐SA produces tolerance or desensitization of opiate actions in the rat brain, which may in turn potentiate drug SA behavior and drug intake. Magn Reson Med 52:108–114, 2004. © 2004 Wiley‐Liss, Inc.