Accentuated behavioral sensitization to nicotine in the neonatal ventral hippocampal lesion model of schizophrenia
Accentuated behavioral sensitization to nicotine in the neonatal ventral hippocampal lesion model of schizophrenia
复制标题
DOI：
10.1016/j.neuropharm.2008.03.011
复制
发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Chambers, R. Andrew
中科院分区：
文献类型：
--
作者：
Berg, Sarah A.;Chambers, R. Andrew
精神分裂症患者的吸烟率远远超过一般人群。精神分裂症患者对尼古丁和其他药物成瘾的脆弱性增加可能反映了发育性边缘系统异常对与吸毒相关的行为变化的皮质纹状体调节的影响。患有新生儿腹侧海马病变（NVHL）的大鼠（一种精神分裂症的神经发育模型）先前已被证明对可卡因和乙醇的行为敏感模式发生了改变。本研究通过测试 NVHL 与 SHAM 操作对照组在 3 周内对尼古丁（0.5 mg/kg）或盐水注射（皮下注射）的反应的运动活性，然后在 2 周后向所有大鼠进行尼古丁激发，探讨了 NVHL 中的尼古丁敏感性。在初始注射系列开始时，所有治疗组中注射后运动激活均无法区分。然而，尼古丁而非盐水注射产生渐进致敏作用，这种作用在 NVHL 中更为明显。与 SHAM 相比。在挑战过程中，与未接受过药物治疗的大鼠相比，有尼古丁史的大鼠表现出对尼古丁的运动激活增强，其中 NVHL 尼古丁大鼠总体上表现出最大程度的活动。这些结果表明，NVHL 对尼古丁表现出改变的短期和长期致敏特征，类似于可卡因和乙醇产生的改变的长期致敏特征。总的来说，这些发现表明，精神分裂症的神经发育基础作为一种不自觉的、进行性的神经行为过程，对成瘾药物产生了增强的行为敏感性，与尼古丁、可卡因或酒精独特的急性精神活性特性无关。 (c) 2008 Elsevier Ltd. 保留所有权利。
The prevalence of smoking in schizophrenia patients far exceeds that in the general population. Increased vulnerability to nicotine and other drug addictions in schizophrenia may reflect the impact of developmental limbic abnormalities on cortical-striatal mediation of behavioral changes associated with drug use. Rats with neonatal ventral hippocampal lesions (NVHLs), a neurodevelopmental model of schizophrenia, have previously been shown to exhibit altered patterns of behavioral sensitization to both cocaine and ethanol. This study explored nicotine sensitization in NVHLs by testing locomotor activity of NVHL vs. SHAM-operated controls over 3 weeks in response to nicotine (0.5 mg/kg) or saline injections (s.c.) followed by a nicotine challenge delivered to all rats 2 weeks later. At the beginning of the initial injection series, post-injection locomotor activation was indistinguishable among all treatment groups. However, nicotine but not saline injections produced a progressive sensitization effect that was greater in NVHLs; compared to SHAMs. In the challenge session, rats with previous nicotine history showed enhanced locomotor activation to nicotine when compared to drug naive rats, with NVHL-nicotine rats showing the greatest degree of activity overall. These results demonstrate that NVHLs exhibit altered short- and long-term sensitization profiles to nicotine, similar to altered long-term sensitization profiles produced by cocaine and ethanol. Collectively, these findings suggest the neurodevelopmental underpinnings of schizophrenia produce enhanced behavioral sensitization to addictive drugs as an involuntary and progressive neurobehavioral process, independent of the acute psychoactive properties uniquely attributed to nicotine, cocaine, or alcohol. (c) 2008 Elsevier Ltd. All rights reserved.