Charles E. Schmidt College of Medicine, Department of Biomedical Science, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
Neuropharmacology. 2012 Dec;63(8):1335-45. doi: 10.1016/j.neuropharm.2012.08.016. Epub 2012 Aug 31.
A rat model of the novelty-seeking phenotype predicts vulnerability to the expression of behavioral sensitization to nicotine, where locomotor reactivity to novelty is used to screen experimentally-naïve rats for high (HR) versus low (LR) responders. The present study examines the long-term neuropeptidergic and neuroplastic adaptations associated with the expression of locomotor sensitization to a low dose nicotine challenge and social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR phenotype. Our data show that the expression of behavioral sensitization to nicotine and abstinence-related anxiety are detected in nicotine pre-exposed HRs even across a long (3 wks) abstinence. Moreover, these behavioral effects of nicotine are accompanied by a persistent imbalance between neuropeptide Y and corticotrophin releasing factor systems, and a persistent increase in brain-derived neurotrophic factor (BDNF) and spinophilin mRNA levels in the amygdala. Furthermore, treatment with the cannabinoid receptor 1 antagonist, AM251 (5 mg/kg) during a short (1 wk) abstinence is ineffective in reversing nicotine-induced anxiety, fluctuations in BDNF and spinophilin mRNAs, and the neuropeptidergic dysregulations in the amygdala; although this treatment is effective in reversing the expression of locomotor sensitization to challenge nicotine even after a long abstinence. Interestingly, the identical AM251 treatment administered during the late phase of a long abstinence further augments anxiety and associated changes in BDNF and spinophilin mRNA in the basolateral nucleus of the amygdala in nicotine pre-exposed HRs. These findings implicate long-lasting neuropeptidergic and neuroplastic changes in the amygdala in vulnerability to the behavioral effects of nicotine in the novelty-seeking phenotype.
一种寻求新奇的表型大鼠模型可预测对尼古丁表达行为敏化的易感性，其中对新奇的运动反应用于在实验性未处理的大鼠中筛选高（HR）与低（LR）反应者。本研究检查了与表达对低剂量尼古丁挑战的运动敏化以及慢性间歇性尼古丁暴露后青少年时期社交焦虑样行为相关的长期神经肽和神经可塑性适应，在 LRHR 表型中。我们的数据表明，即使在长时间（3 周）戒断后，尼古丁预暴露的 HR 中也会检测到对尼古丁的行为敏化和戒断相关焦虑的表达。此外，这些尼古丁的行为效应伴随着神经肽 Y 和促肾上腺皮质释放因子系统之间的持续不平衡，以及杏仁核中脑源性神经营养因子（BDNF）和螺旋蛋白 mRNA 水平的持续增加。此外，在短时间（1 周）戒断期间用大麻素受体 1 拮抗剂 AM251（5mg/kg）治疗不能有效逆转尼古丁引起的焦虑、BDNF 和螺旋蛋白 mRNA 的波动以及杏仁核中的神经肽失调；尽管这种治疗在长时间戒断后甚至对挑战尼古丁的运动敏化的表达有效。有趣的是，在长时间戒断的后期给予相同的 AM251 治疗会进一步增加尼古丁预暴露 HR 中杏仁核基底外侧核的焦虑和相关的 BDNF 和螺旋蛋白 mRNA 变化。这些发现表明杏仁核中的长期神经肽和神经可塑性变化易感性与寻求新奇的表型中尼古丁的行为效应有关。
