Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats.
Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats.
复制标题
早期估计和治疗成瘾脆弱性：新生腹侧海马病变大鼠可卡因致敏或尼古丁自我给药前的径向臂迷宫和 N-乙酰半胱氨酸。
DOI：
10.1007/s00213-016-4421-8
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发表时间：
2016
影响因子：
3.4
通讯作者：
Chambers,RAndrew
中科院分区：
文献类型：
--
作者：
Rao,KalyanN;Sentir,AlenaM;Engleman,EricA;Bell,RichardL;Hulvershorn,LeslieA;Breier,Alan;Chambers,RAndrew
大脑前额叶皮层（PFC）-海马-纹状体回路，通过多巴胺能信号相互连接，在涉及成瘾易损性的精神疾病中功能障碍。ObjectivesIn健康和神经发育改变的大鼠，我们研究了桡臂迷宫（RAM）表现如何估计成瘾易损性，以及如何启动多巴胺能调节剂，青春期的N-乙酰半胱氨酸（NAC）改变成年精神疾病和/或成瘾表型。手术对照组在青春期随机接受NAC和生理盐水，随后在成年早期进行认知测试（RAM），然后进行可卡因行为敏化（实验1;n= 80）或尼古丁自我给药（实验2;结果实验1中NVHL大鼠表现为过度摄食（Froot-Loops（FL））诱导具有较差工作记忆（低臂重复条目（ETR））的RAM，产生升高的FL与ETR比率（“FLETR”;p< 0.001）。与FL或ETR相比，FLETR是可卡因长期致敏程度的最佳线性估计值（R2= 0.14，p < 0.001）。NAC治疗不改变FL、ETR、FLETR或可卡因致敏性。在实验2中，FLETR也与尼古丁诱发的自我给药消退后的复吸过程中随后的药物寻求显著且唯一相关（R2= 0.47，p < 0.01）。NAC没有改变RAM的性能，但显着扭转NVHL诱导的尼古丁寻求在灭绝和restoration.ConclusionsThese研究结果表明，实用程序的精神疾病与成瘾的脆弱性，开发新的诊断措施PFC-海马-纹状体电路功能障碍，可能反映成瘾风险的动物模型。这些测试可以指导成年前的药物治疗和成瘾药物暴露，以预防或治疗成人成瘾。
RationalPrefrontal cortical (PFC)–hippocampal–striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability.ObjectivesIn healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes.MethodsRats with neonatal ventral hippocampal lesions (NVHL) vs. SHAM-operated controls were randomized to NAC vs. saline in adolescence followed by cognitive testing (RAM) in early adulthood and then cocaine behavioral sensitization (experiment 1;n= 80) or nicotine self-administration (experiment 2;n= 12).ResultsIn experiment 1, NVHL rats showed over-consumption of food (Froot-Loops (FL)) baiting the RAM with poor working memory (low-arm entries to repeat (ETR)), producing an elevated FL to ETR ratio (“FLETR”;p< 0.001). FLETR was the best linear estimator (compared to FL or ETR) of magnitude of long-term cocaine sensitization (R2= 0.14,p< 0.001). NAC treatment did not alter FL, ETR, FLETR, or cocaine sensitization. In experiment 2, FLETR also significantly and uniquely correlated with subsequent drug seeking during nicotine-induced reinstatement after extinction of nicotine self-administration (R2= 0.47,p< 0.01). NAC did not alter RAM performance, but significantly reversed NVHL-induced increases in nicotine seeking during extinction and reinstatement.ConclusionsThese findings demonstrate the utility of animal models of mental illness with addiction vulnerability for developing novel diagnostic measures of PFC–hippocampal–striatal circuit dysfunction that may reflect addiction risk. Such tests may direct pharmacological treatments prior to adulthood and addictive drug exposure, to prevent or treat adult addictions.