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5-HT1A and α2 adrenergic receptor levels are associated with high anxiety-like patterns and impulsivity in selectively bred Long Evans rats.
Behavioural Brain Research ( IF 2.6 ) Pub Date : 2020-01-30 , DOI: 10.1016/j.bbr.2020.112522
Tim Niedzielak 1 , Rebecca Ravenelle 2 , Marie Joseph 3 , Corey Calhoun 3 , Brooke Plotkin 3 , Raquel Jones 3 , Maria Herrera 3 , S Tiffany Donaldson 3
Affiliation  

Impulsivity and anxiety are psychological traits involved in many aspects of the drug addiction cycle. However, few preclinical models exist for examining both impulsive and anxiety patterns. In the current study, we investigated whether 6th generation 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.

中文翻译:

5-HT1A和α2肾上腺素能受体的水平与选择性饲养Long Evans大鼠的高焦虑样模式和冲动性有关。

冲动性和焦虑性是吸毒成瘾周期许多方面的心理特征。但是,很少有临床前模型可用于检查冲动和焦虑模式。在当前的研究中,我们调查了选择性繁殖高焦虑症(HAn)行为的第六代大鼠是否会显示苯丙胺(AMPH)过度活跃。在同一世代中,我们还确定了汉动物是否会在操作任务中表现出冲动性。低剂量的AMPH(0.5 mg / kg,IP)后,在高架迷宫(EPM)和运动室中对表型为HAn和低焦虑(LAn)的5只雄性Long Evans雄性大鼠进行测试。接下来,将另一组F5动物暴露于低响应率(DRL:30 s)手术时间表的差异强化以评估冲动性。验尸 在内侧前额叶皮层(mPFC),伏伏核(NAc)核和壳中测量5-HT1A和α2肾上腺素能受体蛋白的水平,并在蓝斑蓝斑(LC)和室旁核(PVN)中评估α2肾上腺素能的计数。下丘脑。F5杂种HAn大鼠的开臂时间百分比降低,EPM进入率降低以及AMPH诱导的运动增加。在DRL中,HAn大鼠表现出冲动型态,获得的总奖励较少,相互间的响应时间更长,并且爆发率更高。我们发现,HAn大鼠在mPFC中具有数量更高的5-HT1A受体免疫染色细胞,但在NAc核或壳中与LAn并无差异。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大鼠的LC含量较高,PVN含量较低。总体,
更新日期:2020-01-31
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