Liu Kun Cheng, Li Jun Yi, Xie Wen, Li Li Bo, Zhang Jin, Du Cheng Xue, Zhang Yu Ming, Tan Hui Hui, Wang Hui Sheng, Zhang Li
Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Brain Res. 2016 Nov 1;1650:184-195. doi: 10.1016/j.brainres.2016.09.009. Epub 2016 Sep 8.
The role of dorsal hippocampus (DH) serotonin (5-HT) receptors in memory is unknown, particularly in memory impairment of Parkinson's disease. We tested here effects of activation and blockade of DH 5-HT receptors on working and hippocampus-dependent memories in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced working and hippocampus-dependent memory impairments as measured by the T-maze rewarded alternation and hole-board tests, and decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), DH and amygdala. Intra-DH injection of 5-HT receptor agonist WAY208466 (1.5, 3 and 6µg/rat) did not change choice accuracy and the number of head-dippings when re-exposure to hole-board in sham-operated rats, while 5-HT receptor antagonist SB258585 (4µg/rat) increased choice accuracy and decreased the number of head-dippings. In the lesioned rats, both WAY208466 (3 and 6µg/rat) and SB258585 (2 and 4µg/rat) increased choice accuracy and decreased the number of head-dippings. Neurochemical results showed that intra-DH injection of WAY208466 or SB258585 produced significant effects on DA and noradrenaline (NA) levels in the mPFC (WAY208466: sham-operated, NA -44%; lesioned, DA 522%, NA -47%; SB258585: sham-operated, DA 72%, NA 85%; lesioned, DA -68%), DH (WAY208466: lesioned, DA 427%; SB258585: sham-operated, DA 119%, NA 206%) and amygdala (WAY208466: sham-operated, NA -28%; lesioned, DA 302%; SB258585: sham-operated, NA 183%); however, 5-HT levels in these brain regions were not changed. These findings suggest DA depletion plays a key role in working and hippocampus-dependent memory impairments, and 5-HT receptors in the DH are involved in the regulation of the memories.
背侧海马体（DH）5-羟色胺（5-HT）受体在记忆中的作用尚不清楚，尤其是在帕金森病的记忆损伤方面。我们在此测试了激活和阻断DH 5-HT受体对内侧前脑束单侧6-羟基多巴胺损伤大鼠的工作记忆和海马体依赖性记忆的影响。通过T迷宫奖励交替和洞板试验测量，该损伤导致工作记忆和海马体依赖性记忆受损，并降低了纹状体、内侧前额叶皮质（mPFC）、DH和杏仁核中的多巴胺（DA）水平。在假手术大鼠中，向DH内注射5-HT受体激动剂WAY208466（1.5、3和6μg/大鼠）在再次暴露于洞板时，并未改变选择准确性和探洞次数，而5-HT受体拮抗剂SB258585（4μg/大鼠）提高了选择准确性并减少了探洞次数。在损伤大鼠中，WAY208466（3和6μg/大鼠）和SB258585（2和4μg/大鼠）均提高了选择准确性并减少了探洞次数。神经化学结果表明，向DH内注射WAY208466或SB258585对mPFC中的DA和去甲肾上腺素（NA）水平产生了显著影响（WAY208466：假手术组，NA降低44%；损伤组，DA升高522%，NA降低47%；SB258585：假手术组，DA升高72%，NA升高85%；损伤组，DA降低68%）、DH（WAY208466：损伤组，DA升高427%；SB258585：假手术组，DA升高119%，NA升高206%）和杏仁核（WAY208466：假手术组，NA降低28%；损伤组，DA升高302%；SB258585：假手术组，NA升高183%）；然而，这些脑区中的5-HT水平未发生变化。这些发现表明，DA耗竭在工作记忆和海马体依赖性记忆损伤中起关键作用，并且DH中的5-HT受体参与了记忆的调节。
