Hranilovic Dubravka, Bucan Maja, Wang Yanyan
Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
Behav Brain Res. 2008 Dec 22;195(2):246-50. doi: 10.1016/j.bbr.2008.09.007. Epub 2008 Sep 18.
The dopamine D2 receptor (D2R) system has been implicated in emotional processing which is often impaired in neuropsychiatric disorders. The long (D2L) and the short (D2S) isoforms of D2R are generated by alternative splicing of the same gene. To study differential roles of the two D2R isoforms, D2L-deficient mice (D2L-/-) expressing functional D2S were previously generated. In this study the contribution of D2L isoform to emotional response was investigated by examining behaviors that reflect emotionality (exploratory behavior, anxiety-like behavior and learned helplessness) in D2L-/- and (wild-type) WT mice. While the thigmotactic, locomotor and general components of anxiety in zero maze did not differ among the genotypes, D2L-/- mice displayed significantly lower level of exploration in a hole board and zero maze, and significantly higher increase in latency to escape from a foot-shock after the learned helplessness training, compared with WT mice. These results suggest that D2L may play a more prominent role than D2S in mediating emotional response, such as behavioral reactions to novelty and inescapable stress. Our findings contribute to a better understanding of the molecular and cellular mechanisms underlying emotional responses.
多巴胺D2受体(D2R)系统与情绪加工有关,而情绪加工在神经精神疾病中常常受损。D2R的长亚型(D2L)和短亚型(D2S)是由同一基因的可变剪接产生的。为了研究这两种D2R亚型的不同作用,先前已培育出表达功能性D2S的D2L缺陷小鼠(D2L-/-)。在本研究中,通过检测D2L-/-小鼠和野生型(WT)小鼠中反映情绪的行为(探索行为、焦虑样行为和习得性无助),研究了D2L亚型对情绪反应的贡献。虽然零迷宫中焦虑的趋触性、运动性和一般成分在不同基因型之间没有差异,但与WT小鼠相比,D2L-/-小鼠在洞板和零迷宫中的探索水平显著降低,在习得性无助训练后逃避足部电击的潜伏期显著增加。这些结果表明,在介导情绪反应方面,如对新奇事物和不可避免压力的行为反应,D2L可能比D2S发挥更突出的作用。我们的研究结果有助于更好地理解情绪反应背后的分子和细胞机制。