CFA誘導(dǎo)的大鼠條件位置逃避模型的觀察

馬洋+秦國(guó)華+王銳

【摘要】 目的：大鼠后腳掌注射完全弗氏佐劑（complete freunds adjuvant，CFA）可誘導(dǎo)產(chǎn)生條件位置回避（conditioned place avoidance，C-CPA）反應(yīng)，大鼠經(jīng)過“非痛環(huán)境”/“痛環(huán)境”適應(yīng)后，檢測(cè)形成的C-CPA行為反應(yīng)可持續(xù)多長(zhǎng)時(shí)間。方法：（1）根據(jù)后腳掌注射CFA后觀察痛行為的時(shí)間，將大鼠隨機(jī)分為Day3組、Day5組、Day7組、Day10組、Day14組共五個(gè)實(shí)驗(yàn)組；（2）建立CFA誘導(dǎo)的CPA模型；（3）檢測(cè)各組大鼠CPA反應(yīng)；（4）Western-blot檢測(cè)rACC腦區(qū)痛情緒相關(guān)NMDA受體亞基NR1及磷酸化（p-NR1）的表達(dá)水平。結(jié)果：大鼠后腳掌注射CFA后五組大鼠熱痛行為反應(yīng)隨時(shí)間無明顯變化；CPA反應(yīng)在Day3組、Day5組、Day7組、Day10組大鼠與注射CFA前相比產(chǎn)生了明顯的CPA反應(yīng)，而Day14組的CPA反應(yīng)明顯減弱；同步Western-blot檢測(cè)的p-NR1表達(dá)也呈現(xiàn)了與行為反應(yīng)一致的變化趨勢(shì)。結(jié)論：CFA一次注射與環(huán)境條件化適應(yīng)建立的C-CPA模型建成后可維持至少10 d的時(shí)間，之后CPA反應(yīng)逐漸消失，且NMDA受體NR1亞基磷酸化水平與CPA反應(yīng)的形成有關(guān)。

【關(guān)鍵詞】 完全弗氏佐劑； 環(huán)境適應(yīng)； 條件位置逃避； 前扣帶皮層； NR1磷酸化

【Abstract】 Objective：Rats injected subcutaneously into the hind paw with complete freunds adjuvant（CFA） were acclimated to one side of cage apparatus to induce conditioned place avoidance（CPA） responses.Then we examined how long C-CPA response was sustained.Method：（1）According to the observation time of CFA-injection into the hind paw，the rats were randomly divided into five groups，such as Day3 group，Day5 group，Day7 group，Day10 group and Day14 group.（2）To establish CFA-induced conditioned place avoidance（C-CPA）.（3）Conditioned place avoidance responses were detected in each group.（4） The expression of NR1 subunits and its phosphorylation were measured by Western-blot.Result：CFA-injection into the hind paw induced nociceptive behaviors and CPA responses.The nociceptive behavior had no obvious change in the course of experiment，and the CPA responses in Day3 group，Day5 group，Day7 group and Day10 group compared with the control group，whereas the responses in Day10 group gradually disappeared.The expressions of the phosphorylation of NR1 measured synchronously presented the same trends with CPA responses.Conclusion：C-CPA responses can stably maintain 10 days，then gradually disappeare.And the expression of p-NR1 relates to the formation of CPA responses.

【Key words】 Complete freunds adjuvant； Acclimation； Conditioned place avoidance； Anterior cingulate cortex； Phosphorylation of NR1 subunits

First-authors address：Shanxi Medical University，Taiyuan 030001，China

doi：10.3969/j.issn.1674-4985.2017.29.002

國(guó)際疼痛研究會(huì)（IASP）將疼痛定義為：“一種不愉快的感覺和情緒體驗(yàn)，其發(fā)生與實(shí)際或潛在的組織損傷有關(guān)或這類損傷的相關(guān)描述。”可見，疼痛包含兩種成分：即痛的感覺分辨（sensory-discriminative）和痛的情緒反應(yīng)（emotional-affective dimensions）[1-2]。前者主要感受和編碼刺激的屬性，如刺激的性質(zhì)、強(qiáng)度、定位等；后者指痛的情緒、情感反應(yīng)，涉及編碼傷害性刺激所引發(fā)的厭惡、焦慮、恐懼等負(fù)性情緒。神經(jīng)傳導(dǎo)疼痛的情緒和感覺成分時(shí)有著不同的通路和機(jī)制。有研究表明，ACC和疼痛的情緒方面密切相關(guān)，在ACC內(nèi)，N-甲基-D-天冬氨酸（N-methyl-D-aspartic acid receptor，NMDA）受體是由NR1、NR2及NR3三種不……