5-HT1A and α2 adrenergic receptor levels are associated with high anxiety-like patterns and impulsivity in selectively bred Long Evans rats.
5-HT1A and α2 adrenergic receptor levels are associated with high anxiety-like patterns and impulsivity in selectively bred Long Evans rats.
复制标题
5-HT1A 和α2 肾上腺素能受体水平与选择性繁殖的长埃文斯大鼠的高度焦虑样模式和冲动相关。
DOI：
10.1016/j.bbr.2020.112522
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发表时间：
2020
影响因子：
2.7
通讯作者：
TiffanyDonaldson,S
中科院分区：
文献类型：
--
作者：
Niedzielak,Tim;Ravenelle,Rebecca;Joseph,Marie;Calhoun,Corey;Plotkin,Brooke;Jones,Raquel;Herrera,Maria;TiffanyDonaldson,S
冲动和焦虑是涉及药物成瘾循环许多方面的心理特征。然而，很少有临床前模型存在检查冲动和焦虑模式。在目前的研究中，我们调查了第六代大鼠是否选择性地饲养高焦虑（HAn）样行为，将显示安非他明（AMPH）多动症。在同一世代线，我们还确定了如果汉动物将显示冲动在一个操作性任务。在高架十字迷宫（elevated plus maze，EMAZ）和运动室中测试了表现为HAn和低焦虑（low anxiety，LAn）的5只雄性Long Evans大鼠的子代，在低剂量AMPH（0.5mg/kg，IP）后。接下来，将一组单独的F5动物暴露于低反应率（DRL：30 s）操作性时间表的差异强化，以评估冲动性。处死后，测定内侧前额叶皮质（mPFC）、中脑核（NAc）核芯和壳的5-HT 1A和α2肾上腺素能受体蛋白水平，蓝斑（LC）和室旁核（PVN）的α2肾上腺素能计数。F5远系杂交的HAn大鼠的开放臂时间百分比降低，并且在运动和升高的AMPH诱导的运动上的条目减少。在DRL中，HAn大鼠表现出冲动的特征，他们获得的总奖励较少，有更多的反应时间，并表现出更大的爆发率。我们发现，HAn大鼠有更多的5-HT 1A受体免疫染色细胞的mPFC，但没有不同的NAc核心或壳比LAn。相比之下，mPFC中的α2肾上腺素能受体蛋白水平没有差异，而Han大鼠LC中的α2肾上腺素能受体蛋白水平较高，PVN中的α 2肾上腺素能受体蛋白水平较低。总的来说，这些数据进一步验证了我们的远系杂交特质焦虑大鼠：HAn雄性大鼠表现出焦虑样行为、AMPH超敏反应、更强的冲动性以及不同水平的边缘系统和中脑5-HT 1A和α2肾上腺素能受体蛋白。
Impulsivity and anxiety are psychological traits involved in many aspects of the drug addiction cycle. However, few preclinical models exist for examiningbothimpulsive and anxiety patterns. In the current study, we investigated whether 6thgeneration rats selectively bred for high anxiety (HAn)-like behavior would display amphetamine (AMPH) hyperactivity. In the same generational line, we also determined if HAn animals would display impulsivity in an operant task. Filial 5 male Long Evans rats phenotyped as HAn and low anxiety (LAn) were tested on the elevated plus maze (EPM) and in locomotor chambers following a low dose of AMPH (0.5 mg/kg, IP). Next, a separate group of F5 animals was exposed to a differential reinforcement of low rate of responding (DRL: 30 s) operant schedule to assess impulsivity. Postmortem, 5-HT1A and α2 adrenergic receptor protein levels were measured in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) core and shell, and α2 adrenergic counts were assessed in the locus coeruleus (LC), and the paraventricular nucleus (PVN) of the hypothalamus. F5 outbred HAn rats had decreased percent open arm time and entries on the EPM and elevated AMPH-induced locomotion. In the DRL, HAn rats displayed an impulsive profile, they attained fewer total rewards, had more inter-response times, and showed greater burst ratios. We found that HAn rats had a higher number of 5-HT1A receptor immunostained cells in the mPFC but were not different than LAn in NAc core or shell. By contrast, levels of the α2 adrenergic receptor protein were no different in the mPFC while HAn rats had greater levels in the LC and lower levels in the PVN. Overall, these data further validate our outbred trait anxiety rats: HAn males show anxiety-like behavior, AMPH hypersensitivity, greater impulsivity, and varying levels of limbic and midbrain 5-HT1A and α2 adrenergic receptor proteins.