Cocaine-induced metabolic activation in cortico-limbic circuitry is increased after exposure to the histone deacetylase inhibitor, sodium butyrate.
Cocaine-induced metabolic activation in cortico-limbic circuitry is increased after exposure to the histone deacetylase inhibitor, sodium butyrate.
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DOI：
10.1016/j.neulet.2009.07.065
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发表时间：
2009-11-20
影响因子：
2.5
通讯作者：
Ferris CF
中科院分区：
文献类型：
--
作者：
Febo M;Akbarian S;Schroeder FA;Ferris CF
药物诱导的组蛋白脱乙酰酶(HDAC)抑制导致暴露于可卡因和其他兴奋剂滥用药物引起的许多行为变化的改变，但缺乏涉及的神经元回路的全面图谱。本研究利用清醒大鼠的血氧水平依赖功能磁共振成像(BOLD FMRI)来确定HDAC抑制剂丁酸钠(SBT)在可卡因反复给药初期对大脑代谢激活模式的影响。三组大鼠在BOLD fMRI期间接受可卡因，(I)第一次急性注射，或(II)生理盐水或(III)SBT在可卡因之前30分钟预处理两天。急性但不重复地接触可卡因导致了前脑和中脑广泛的大胆激活。在反复接触可卡因后，SBT预处理恢复了前脑中的BOLD信号，包括丘脑前部、海马体/杏仁核以及边缘和感觉皮质的不同部分的显著激活。边缘中皮质区域也有类似的变化趋势，但未达到统计学意义。这些发现表明，在反复接触刺激剂后，HDACi的调制涉及调节情绪、动机和记忆的皮质-边缘回路。
Drug-induced inhibition of histone deacetylase (HDAC) results in the modification of many behavioral changes resulting from exposure to cocaine and other stimulant drugs-of-abuse, but a comprehensive map of the neuronal circuitries involved is lacking. The present study used blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) in awake rats to determine the effects of the HDAC inhibitor, sodium butyrate (SBt) on brain metabolic activation patterns during the initial stage of repeated cocaine administration. Three groups of rats received cocaine during BOLD fMRI, (i) acutely for the first time, or pretreated for two days with either (ii) saline or (iii) SBt 30 min prior to cocaine. Acute but not repeated exposure to cocaine resulted in widespread BOLD activation in fore- and midbrain. Pretreatment with SBt restored BOLD signals in the forebrain after repeated cocaine exposure, including a pronounced activation in the anterior thalamus, the hippocampus/amygdala and various portions of limbic and sensory cortex. Mesocorticolimbic areas showed a similar trend, but did not reach statistical significance. These findings suggest that HDACi modulation after repeated stimulant exposure involves cortico-limbic circuitry regulating emotion, motivation and memory.
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