張 霞 雷 怡 王福順

催產(chǎn)素、孕激素和雌激素對(duì)厭惡的影響及其神經(jīng)生理機(jī)制*

張 霞 雷 怡 王福順

(四川師范大學(xué)腦與心理科學(xué)研究院, 成都 610066)

厭惡是人和動(dòng)物最基本的情緒之一, 起源于口腔對(duì)苦味(有毒)物質(zhì)的排斥, 常伴有惡心嘔吐和遠(yuǎn)離誘發(fā)刺激的強(qiáng)烈愿望, 具有回避潛在疾病威脅的功能。大量動(dòng)物和人類研究表明, 催產(chǎn)素、孕激素和雌激素不同程度地影響核心厭惡刺激的感知、核心厭惡情緒的產(chǎn)生與表達(dá)、條件性厭惡習(xí)得和厭惡表情識(shí)別。三種激素主要通過作用于五羥色胺、γ-氨基丁酸、乙酰膽堿和谷氨酸等神經(jīng)遞質(zhì)受體, 調(diào)節(jié)杏仁核、腦島、前扣帶回、殼核、梨狀皮層、額中回等腦區(qū)活動(dòng), 影響厭惡加工。未來研究應(yīng)當(dāng)在準(zhǔn)確測(cè)量激素水平和控制實(shí)驗(yàn)任務(wù)難度的基礎(chǔ)上, 探究各激素對(duì)不同感覺通道厭惡加工的影響, 及其性別的調(diào)節(jié)作用; 同時(shí)結(jié)合腦成像技術(shù)和動(dòng)物行為學(xué), 明確各激素影響厭惡加工的神經(jīng)內(nèi)分泌機(jī)制。

厭惡, 催產(chǎn)素, 孕激素, 雌激素, 神經(jīng)生理機(jī)制

1 引言

基本情緒是進(jìn)化而來的對(duì)外部刺激的適應(yīng)性反應(yīng), 其最基本的作用就是讓個(gè)體能在所處環(huán)境中找到食物(愉快), 躲避捕食者(恐懼), 避免被感染(厭惡), 進(jìn)而在群體中“活”下來(Darwin & Prodger, 1998; Weinstein et al., 2018)。在生活中, 嘔吐物、排泄物、腐爛物、某些動(dòng)物(蛆、蒼蠅等)、臟亂環(huán)境(垃圾場、廁所等)和不文明行為(亂丟垃圾、隨地吐痰等)都會(huì)誘發(fā)厭惡情緒(雷怡等, 2019)。厭惡情緒涉足人類生活的多個(gè)方面。研究發(fā)現(xiàn), 厭惡在行為免疫系統(tǒng)中扮演著重要角色, 能夠調(diào)節(jié)對(duì)病原體相關(guān)刺激和行為的回避, 降低被感染的風(fēng)險(xiǎn)(Cepon-Robins et al., 2021)。在新型冠狀病毒肺炎正在全球大規(guī)模爆發(fā)的背景下, 高厭惡敏感性誘發(fā)的行為改變(如保持社交距離、洗手、消毒等)能有效阻止疫情進(jìn)一步擴(kuò)散(Shook et al., 2020)。除了公共健康, 厭惡情緒還影響道德判斷(Bia?ek et al., 2021)、政治決策(Shook et al., 2017)和種系發(fā)展(O'Shea et al., 2019)等, 故對(duì)厭惡情緒的深入研究對(duì)個(gè)體生存和社會(huì)發(fā)展都具有重大意義。

目前對(duì)厭惡的研究主要包括：厭惡的結(jié)構(gòu)與分類(Stevenson et al., 2019); 厭惡的進(jìn)化功能(Oaten et al., 2009); 厭惡表情識(shí)別(Wicker et al., 2003); 條件性厭惡習(xí)得與表達(dá)(Schier et al., 2019); 厭惡與其他基本情緒的關(guān)系, 如厭惡與恐懼(Weinstein et al., 2018)、厭惡與憤怒(Molho et al., 2017); 以及厭惡與恐懼癥、強(qiáng)迫癥、進(jìn)食障礙等精神類疾病的關(guān)系(Khalil et al., 2020; Knowles et al., 2018)等。此外, 激素是否以及如何調(diào)節(jié)厭惡加工也是重要研究內(nèi)容, 這有助于我們深入了解厭惡情緒的進(jìn)化意義以及厭惡產(chǎn)生的神經(jīng)生理基礎(chǔ)。

厭惡情緒的產(chǎn)生與表達(dá)涉及到多種激素參與, 包括催產(chǎn)素、孕激素、雌激素、睪酮、皮質(zhì)類固醇、精氨酸加壓素等, 這些不同的神經(jīng)內(nèi)分泌調(diào)節(jié)系統(tǒng)能夠使個(gè)體獲得與毒素、病原體線索有關(guān)的信息, 并在此基礎(chǔ)上進(jìn)行評(píng)估、整合, 從而產(chǎn)生相應(yīng)的厭惡情緒與回避行為(Kavaliers, Ossenkopp, et al., 2019)。其中, 催產(chǎn)素、孕激素和雌激素是當(dāng)前厭惡領(lǐng)域研究最廣泛的激素。

基于以上內(nèi)容, 本文將對(duì)厭惡情緒的含義, 催產(chǎn)素、孕激素和雌激素影響厭惡加工的證據(jù), 以及三種激素影響厭惡加工的神經(jīng)機(jī)制三個(gè)方面的最新研究進(jìn)行探討; 旨在明確厭惡情緒的進(jìn)化意義, 探究三種激素影響厭惡情緒加工的神經(jīng)生理機(jī)制, 以進(jìn)一步了解厭惡情緒與內(nèi)分泌系統(tǒng)的關(guān)系。

2 厭惡情緒

厭惡源于口腔對(duì)苦味物質(zhì)的排斥, 苦味常表明含有大量有毒的生物堿, 故厭惡最基本的功能是清除口腔中的有毒物質(zhì), 避免對(duì)機(jī)體造成傷害(Rozin et al., 2016)。隨著進(jìn)化演變, 為避免疾病消耗巨大的健康成本, 個(gè)體對(duì)細(xì)菌、病毒和寄生蟲等病原體線索刺激產(chǎn)生厭惡, 進(jìn)而觸發(fā)回避行為, 避免被感染, 使得厭惡成為一種疾病回避機(jī)制(Oaten et al., 2009; Weinstein et al., 2018)。這種特性具有物種上的延續(xù)性, 從龍蝦、蝌蚪、螞蟻、蜜蜂、蝸牛、魚類、鳥類、嚙齒動(dòng)物、非人類靈長類動(dòng)物到人類都會(huì)對(duì)感染了病原體的同伴產(chǎn)生厭惡反應(yīng)(Behringer et al., 2006; Kavaliers et al., 2020; Kiesecker et al., 1999)。綜上而言, 厭惡是在進(jìn)化中形成的一種“行為免疫”, 通過檢測(cè)有毒物質(zhì)和病原體相關(guān)線索, 誘發(fā)回避行為(如惡心、嘔吐、食欲降低)來驅(qū)除體內(nèi)的毒素、病菌和寄生蟲等有害物質(zhì), 或降低攝入它們的風(fēng)險(xiǎn), 以免個(gè)體中毒或感染疾病。

隨著人類認(rèn)知的發(fā)展, 厭惡與社會(huì)文化產(chǎn)生交互作用, 使厭惡對(duì)象逐步泛化。研究者們根據(jù)誘發(fā)刺激的特點(diǎn)對(duì)厭惡進(jìn)行了更細(xì)致的分類。Rozin和Fallon (1987)將厭惡分成了5類：(1)苦或酸類物質(zhì)引起的口腔反應(yīng); (2)核心厭惡(core disgust), 由某些食物(如腐爛的肉類)、身體分泌物(如糞便)和特定動(dòng)物(如蒼蠅)誘發(fā); (3)動(dòng)物提醒厭惡(animal-nature reminder disgust), 由讓個(gè)體意識(shí)到人類只是動(dòng)物的事實(shí)所誘發(fā), 如身體損傷、不衛(wèi)生行為和死亡等; (4)人際厭惡(interpersonal disgust), 由攜帶病原體或者受歧視的群體(如傳染病患者、殘疾人)誘發(fā); (5)道德厭惡(moral disgust), 由不符合道德規(guī)范或讓人感到墮落、卑賤的行為誘發(fā)。之后, Olatunji等人(2009)在Rozin的基礎(chǔ)上進(jìn)行修改, 提出三個(gè)主要類別：核心厭惡、動(dòng)物提醒厭惡和污染厭惡(contamination disgust), 其中污染厭惡指中性物體與厭惡誘發(fā)物(如糞便)接觸后, 中性物體也讓人感到厭惡。此外, Tybur等人(2013)在進(jìn)化的基礎(chǔ)上, 重新構(gòu)建了之前的厭惡理論, 提出了三域厭惡理論：病原體厭惡(pathogen disgust)、性厭惡(sex disgust)和道德厭惡。病原體厭惡是指面臨細(xì)菌、病毒或寄生蟲等病原體感染時(shí)誘發(fā)的厭惡, 如摸到糞便; 性厭惡由不適宜的性行為激發(fā), 如亂倫。雖不同研究者對(duì)厭惡分類各有不同, 但各厭惡類型之間存在交叉重疊, 例如人際厭惡、動(dòng)物提醒厭惡、性厭惡和污染厭惡都可能包含病原體線索。故在實(shí)際研究中, 研究者更多地將厭惡簡單分為核心厭惡和道德厭惡。核心厭惡反映了對(duì)可能間接傳播疾病的媒介的回避, 如腐爛的食物、排泄物、蒼蠅和蟑螂等動(dòng)物, 等同于病原體厭惡; 道德厭惡由違反社會(huì)規(guī)范誘發(fā), 后者比前者更抽象, 涉及更多的社會(huì)認(rèn)知(Moran et al., 2019)。Chapman等人(2009)發(fā)現(xiàn)道德厭惡起源于口腔, 與討厭的味道和潛在致病線索誘發(fā)的厭惡相似, 故道德厭惡可能是在核心厭惡基礎(chǔ)上形成的社會(huì)性情緒。

厭惡加工涉及厭惡刺激、厭惡評(píng)價(jià)系統(tǒng)和厭惡輸出三個(gè)層面, 核心厭惡刺激可直接觸發(fā)厭惡輸出, 而道德厭惡必須經(jīng)過評(píng)價(jià)系統(tǒng)產(chǎn)生, 再通過表情(如鼻皺、張口)、行為(如撤離)和生理反應(yīng)(如惡心)表達(dá)(Rozin et al., 2009)。這些特定的表達(dá)將外部空間與個(gè)體內(nèi)部隔離, 有助于減少有害物質(zhì)輸入或排出口腔中的污染物質(zhì), 從而起到保護(hù)作用。厭惡的三級(jí)加工表明厭惡情緒源于先天本能, 但更多的厭惡反應(yīng)是后天學(xué)習(xí)的結(jié)果, 與社會(huì)認(rèn)知密切相關(guān)。

總之, 厭惡情緒具有回避疾病的功能, 是人和動(dòng)物共同擁有的幾種最原始的基本情緒之一。同時(shí), 它又受社會(huì)文化的塑造, 與“干凈”、“純潔”密切相關(guān), 任何違反這些屬性的物體、行為或觀念都可能誘發(fā)厭惡情緒, 產(chǎn)生厭惡時(shí)通常伴有惡心感和遠(yuǎn)離誘發(fā)刺激的強(qiáng)烈愿望, 并具有獨(dú)特保護(hù)性的面部表情和生理反應(yīng)。

3 催產(chǎn)素影響厭惡加工及其神經(jīng)機(jī)制

3.1 催產(chǎn)素影響厭惡加工

3.1.1 動(dòng)物實(shí)驗(yàn)

動(dòng)物通常借助嗅覺識(shí)別被寄生蟲感染的同類, 產(chǎn)生病原體厭惡和回避行為, 從而避免被感染(Kavaliers et al., 2020)。研究發(fā)現(xiàn), 催產(chǎn)素(oxytocin, OT)能夠調(diào)節(jié)嚙齒動(dòng)物病原體相關(guān)的厭惡反應(yīng)和回避行為。例如, 使用OT拮抗劑會(huì)減弱雄性小鼠對(duì)被感染雌性小鼠的回避(Kavaliers, Colwell, et al., 2019); 催產(chǎn)素基因敲除小鼠分辨健康小鼠和被感染小鼠氣味的能力受損, 對(duì)被感染小鼠的厭惡反應(yīng)減弱(Kavaliers et al., 2004)。這表明OT可能通過提高識(shí)別病原體的能力, 增強(qiáng)厭惡反應(yīng)來避免疾病侵害(Kavaliers & Choleris, 2011)。同時(shí), 在不熟悉的環(huán)境或暴露于被感染同類誘發(fā)的應(yīng)激反應(yīng)中, OT能促進(jìn)小鼠對(duì)陌生同類的厭惡和回避反應(yīng)(Duque-Wilckens et al., 2018; Kavaliers, Colwell, et al., 2019)。Duque-Wilckens等人(2018)認(rèn)為OT產(chǎn)生的這種社交抑制不是降低了社交動(dòng)機(jī), 而是提高了對(duì)陌生的、具有威脅性的社交環(huán)境的警惕, 包括那些與病原體和毒素有關(guān)的環(huán)境。這表明OT可能促進(jìn)動(dòng)物對(duì)病原體線索的感知與識(shí)別, 增強(qiáng)核心厭惡反應(yīng), 從而參與病原體相關(guān)的配偶選擇、群體內(nèi)偏見和群體外回避的調(diào)節(jié)。

此外, OT還與毒素引起的條件性厭惡的習(xí)得與表達(dá)有關(guān)。注射OT拮抗劑, 可減弱雄性大鼠對(duì)毒素氯化鋰(LiCl)的厭惡, 降低對(duì)雌性伴侶的主動(dòng)接觸(Boulet et al., 2016)。Verbalis等人(1986)發(fā)現(xiàn)大鼠在受到LiCl和CuSO4(硫酸銅)的刺激產(chǎn)生味覺厭惡的同時(shí), 會(huì)分泌催產(chǎn)素。進(jìn)一步研究發(fā)現(xiàn), LiCl誘導(dǎo)的條件性味覺厭惡(conditioned taste aversion)與OT神經(jīng)元激活有關(guān), 且注射OT拮抗劑, 可損害小鼠條件性味覺厭惡的習(xí)得(Olszewski et al., 2013)。這表明OT很可能參與了動(dòng)物的味覺厭惡學(xué)習(xí), 但由于缺乏對(duì)其他感覺通道的研究, 故還不清楚OT對(duì)動(dòng)物厭惡學(xué)習(xí)的影響是否具有跨感覺通道一致性。

3.1.2 人體實(shí)驗(yàn)

在人類研究中, Declerck等人(2014)發(fā)現(xiàn)鼻內(nèi)OT給藥降低了女性對(duì)骯臟、充滿細(xì)菌環(huán)境圖片的厭惡感, 但對(duì)男性沒產(chǎn)生影響; 同時(shí), 接受OT給藥的男性更傾向于將面孔評(píng)估為不健康, 但在女性上沒有發(fā)現(xiàn)該趨勢(shì)。這表明外源性O(shè)T給藥沒有促進(jìn)基于視覺線索的病原體檢測(cè), 且對(duì)健康和疾病線索的感知上表現(xiàn)出明顯的性別差異。該研究作者認(rèn)為女性厭惡感降低可能是由于OT緩解了被感染的焦慮。此結(jié)果似乎與OT增強(qiáng)嚙齒動(dòng)物病原體厭惡的結(jié)果相矛盾, 可能是因?yàn)橛脠D片代替真實(shí)感染環(huán)境, 剝奪了被試的嗅覺感官, 表明OT可能對(duì)產(chǎn)生核心厭惡的視覺線索和嗅覺線索具有不同影響。

面部表情識(shí)別是社交中不可缺少的部分, 一項(xiàng)元分析研究發(fā)現(xiàn)鼻內(nèi)OT給藥能改善基本情緒面孔(尤其是厭惡和恐懼)的識(shí)別(Leppanen et al., 2017)。在趨近?回避運(yùn)動(dòng)反應(yīng)中發(fā)現(xiàn), OT同時(shí)增強(qiáng)了對(duì)厭惡面孔的趨近和回避反應(yīng), 但對(duì)憤怒、恐懼、悲傷和愉快面孔沒有影響, 表明OT加快了厭惡面孔加工, 增強(qiáng)了厭惡刺激顯著性(Theodoridou et al., 2013)。在表情識(shí)別任務(wù)中, 同樣發(fā)現(xiàn)鼻內(nèi)OT給藥提高了對(duì)厭惡面孔的厭惡強(qiáng)度評(píng)分, 但降低了厭惡面孔識(shí)別的準(zhǔn)確性(Cardoso et al., 2014)。該作者認(rèn)為OT降低厭惡面孔識(shí)別準(zhǔn)確度, 可能是由于OT將注意力集中在眼部區(qū)域, 而只通過眼睛很難識(shí)別厭惡表情。之前也有研究發(fā)現(xiàn)OT會(huì)減少對(duì)厭惡面孔的注意偏向(Kim et al., 2014), 增加對(duì)眼睛區(qū)域的注視(Wang et al., 2020)。故OT降低厭惡面孔識(shí)別的準(zhǔn)確性可能與OT對(duì)注意力的調(diào)節(jié)有關(guān)。

OT是否影響道德厭惡, 還缺少直接的實(shí)證研究證據(jù)。但已有研究發(fā)現(xiàn)不管是催產(chǎn)素基因變異, 還是外源性O(shè)T注入都會(huì)影響道德判斷(Bernhard et al., 2016; Scheele et al., 2014)。故OT很可能在道德厭惡中起作用, 但還有待進(jìn)一步論證。

3.2 催產(chǎn)素影響厭惡加工的神經(jīng)機(jī)制

神經(jīng)肽催產(chǎn)素在下丘腦視上核(supraoptic nucleus, SON)和室旁核(paraventricular nucleus, PVN)中合成, 其受體在腦島、杏仁核、前扣帶回、梨狀皮層等腦區(qū)高度表達(dá), 廣泛參與情緒和社會(huì)行為的加工(Boccia et al., 2013)。

人類聞到厭惡氣味, 識(shí)別厭惡面孔都會(huì)激活腦島(insula) (Wicker et al., 2003)。用電或光刺激小鼠、猴子和人類前腦島, 會(huì)產(chǎn)生惡心嘔吐, 表現(xiàn)出上嘴唇上提、鼻皺等典型的厭惡表情(Caruana et al., 2011; Dolensek et al., 2020; Mazzola et al., 2017)。Berret等人(2019)發(fā)現(xiàn)抑制后腦島會(huì)消除小鼠對(duì)足部電擊的厭惡, 表明腦島參與厭惡的軀體感覺信息加工, 并將該信息傳遞到杏仁核特定區(qū)域。綜上而言, 腦島在厭惡的識(shí)別、體驗(yàn)和表達(dá)中發(fā)揮著關(guān)鍵作用。研究發(fā)現(xiàn), OT受體在腦島中分布密度較高, 腦島接收PVN中OT軸突的輸入信息, 增強(qiáng)腦島內(nèi)的興奮性、突觸效能及其功能連接, 調(diào)節(jié)對(duì)社會(huì)情感刺激的趨近和回避(Rogers-Carter et al., 2018; Yao et al., 2018)。人類在評(píng)價(jià)情緒面孔的喚醒度時(shí), 鼻內(nèi)OT給藥后增強(qiáng)了腦島對(duì)厭惡面孔的反應(yīng)(Scheele et al., 2014)。OT或許通過增加腦島活動(dòng), 來提升對(duì)厭惡面孔的感知強(qiáng)度, 但還不能確定對(duì)非社會(huì)性厭惡刺激是否有相似的作用。此外, 有研究發(fā)現(xiàn)腦島中的五羥色胺(serotonin, 5-HT)參與預(yù)期厭惡的調(diào)節(jié), 是厭惡學(xué)習(xí)形成的關(guān)鍵(Limebeer et al., 2018; Tuerke et al., 2012)。釋放5-HT產(chǎn)生惡心的同時(shí), OT可以調(diào)節(jié)5-HT受體的活性(Mottolese et al., 2014; Tuerke et al., 2012)。因此, OT可能在腦島中通過影響5-HT, 促進(jìn)厭惡學(xué)習(xí)及其厭惡情緒相關(guān)的行為反應(yīng)。

前扣帶回(anterior cingulate cortex, ACC)涉及多模態(tài)厭惡刺激加工, 包括輕微電擊、厭惡的味道、聲音、表情、氣味, 甚至不公平待遇(Amir et al., 2005; Corradi-Dell’Acqua et al., 2016; Schr?der et al., 2019; Wicker et al., 2003)。研究發(fā)現(xiàn), 小鼠ACC神經(jīng)元優(yōu)先編碼代表社會(huì)性厭惡線索的信息, 再將該信息傳遞到基底外側(cè)杏仁核(Allsop et al., 2018); 急性O(shè)T給藥能增強(qiáng)小鼠ACC的細(xì)胞活性(Pisansky et al., 2017)。在閾下情緒面孔加工的fMRI研究中發(fā)現(xiàn), OT減弱了女性加工厭惡面孔時(shí)ACC與杏仁核之間的功能連接(Luo et al., 2017)。由此可見, OT可能通過影響ACC的活動(dòng)以及ACC與其他腦區(qū)的功能連接參與社會(huì)性厭惡信息的編碼。

杏仁核(amygdala)接受來自腦島和ACC傳來的厭惡線索信息(Allsop et al., 2018; Berret et al., 2019), 并投射到其他相關(guān)腦區(qū)(如基底核黑質(zhì))參與厭惡加工(Steinberg et al., 2020)。研究發(fā)現(xiàn), OT是條件性味覺厭惡習(xí)得的關(guān)鍵, 阻斷OT受體會(huì)減弱杏仁核對(duì)厭惡刺激的反應(yīng)(Olszewski et al., 2013)。在厭惡面孔識(shí)別中, 也發(fā)現(xiàn)OT增強(qiáng)右側(cè)杏仁核對(duì)厭惡面孔的反應(yīng)(Yao et al., 2018)。這不同于OT減弱杏仁核對(duì)恐懼、憤怒等消極情緒刺激的反應(yīng)(Wang et al., 2017), 表明在加工厭惡情緒時(shí), OT可能對(duì)杏仁核有特殊影響, 也側(cè)面反映出厭惡是一種獨(dú)特的情緒, 與其他負(fù)性情緒之間存在差異。

在其他腦區(qū)也發(fā)現(xiàn)了OT調(diào)節(jié)厭惡加工的證據(jù)。例如, 厭惡與嗅覺密切相關(guān), Choe等人(2015)發(fā)現(xiàn)參與嗅覺加工的梨狀皮層(piriform cortex)中含有大量的OT受體, OT可以通過直接調(diào)節(jié)梨狀皮層的活動(dòng), 在食欲和厭惡的社會(huì)性氣味學(xué)習(xí)中發(fā)揮重要作用。亨廷頓氏癥(huntington's disease, HD)患者最典型的特征就是不能識(shí)別厭惡面孔, 鼻內(nèi)OT能增強(qiáng)HD患者殼核(putamen)和額中回(middle frontal gyri)活動(dòng), 進(jìn)而提高HD患者對(duì)厭惡面孔的識(shí)別能力, 但OT降低了正常被試殼核和額中回對(duì)厭惡面孔的反應(yīng)(Labuschagne et al., 2018)。這表明OT可能通過某種平衡機(jī)制參與維持厭惡面孔識(shí)別正?；? 濫用OT將對(duì)厭惡刺激識(shí)別產(chǎn)生抑制作用。

此外, 研究發(fā)現(xiàn)OT給藥會(huì)減弱正常個(gè)體杏仁核與腦島、ACC的功能連接(Gorka et al., 2015)。加工厭惡面孔時(shí), OT減弱了女性右側(cè)杏仁核與左側(cè)ACC之間的功能連接(Luo et al., 2017)。這表明OT可能同時(shí)影響多個(gè)共同參與厭惡加工的腦區(qū)活動(dòng)。

綜上, 催產(chǎn)素可以對(duì)腦島、前扣帶回、杏仁核、梨狀皮層、殼核、額中回等多個(gè)腦區(qū)活動(dòng)產(chǎn)生影響, 進(jìn)而參與厭惡情緒的加工。

4 孕激素影響厭惡加工及其神經(jīng)機(jī)制

4.1 孕激素影響厭惡加工

4.1.1 動(dòng)物實(shí)驗(yàn)

來自人類研究的證據(jù)表明孕激素影響病原體厭惡后, Kavaliers等人(2021a)首次在動(dòng)物身上進(jìn)行了驗(yàn)證, 他們?cè)诩毙栽屑に亟o藥后, 觀察了發(fā)情雌性小鼠對(duì)感染線蟲的雄性小鼠氣味的厭惡反應(yīng), 但結(jié)果發(fā)現(xiàn)孕激素不影響雌性小鼠的病原體厭惡及其回避行為。但實(shí)驗(yàn)中沒有注射孕酮的對(duì)照組小鼠的回避反應(yīng)已經(jīng)非常強(qiáng), 其結(jié)果不顯著可能是受到反應(yīng)指標(biāo)天花板效應(yīng)的干擾。此外, Bressan和Kramer (2021)認(rèn)為Kavaliers等人的數(shù)據(jù)分析也存在不妥, 采用更敏感的方法重新分析數(shù)據(jù)后發(fā)現(xiàn), 急性孕酮治療組的小鼠接觸被感染雄性氣味的時(shí)間顯著減少, 證明孕激素可以提高病原體厭惡, 并增強(qiáng)對(duì)病原體線索的回避。

病原體厭惡及其回避行為的產(chǎn)生涉及到三個(gè)過程：(1)感覺輸入和社會(huì)信息的感知、接收和突顯; (2)多模態(tài)感覺輸入的整合和加工; (3)將病原體線索轉(zhuǎn)為喚醒, 并決定與誰互動(dòng)和避免誰(Kavaliers et al., 2021b)。雖然現(xiàn)有研究證實(shí)了孕激素對(duì)病原體厭惡的促進(jìn)作用, 但仍不清楚孕激素在哪個(gè)加工過程中產(chǎn)生影響, 未來可進(jìn)行細(xì)化研究。

最后, 在嚙齒動(dòng)物的厭惡學(xué)習(xí)中, 并未發(fā)現(xiàn)孕激素影響條件性味覺厭惡的習(xí)得與消退(Chambers, 1980; Lin et al., 2015)。

4.1.2 人體實(shí)驗(yàn)

孕酮(progesterone)是人體中最重要的孕激素, 也是一種已知的免疫抑制劑, 通過調(diào)節(jié)一系列生理反應(yīng), 最終導(dǎo)致疾病易感性增加(Shah et al., 2018)。免疫力越弱的個(gè)體對(duì)厭惡刺激越敏感, 傾向于回避潛在的健康威脅, 產(chǎn)生行為免疫(Murray et al., 2019)。“補(bǔ)償性預(yù)防假說” (the compensatory prophylaxis hypothesis)認(rèn)為妊娠期間母體為防止自身免疫攻擊囊胚或胚胎, 會(huì)適應(yīng)性上調(diào)孕激素水平產(chǎn)生免疫抑制; 但為降低感染風(fēng)險(xiǎn), 孕婦會(huì)提高對(duì)潛在感染刺激的厭惡敏感性, 補(bǔ)償孕激素引起的免疫應(yīng)答減少(Ackerman et al., 2018; Fessler et al., 2005)。在有關(guān)女性月經(jīng)周期的研究中, 驗(yàn)證了孕激素與病原體厭惡的密切關(guān)系。例如, 女性在黃體中期(高孕酮)對(duì)惡心圖片的注視時(shí)間顯著低于卵泡早期(低孕酮), 表明黃體中期個(gè)體厭惡敏感性更高, 對(duì)厭惡刺激的回避更強(qiáng)(Pilarczyk et al., 2019)。量表測(cè)量也得到了一致結(jié)果, 受感染女性黃體期病原體厭惡得分顯著高于卵泡期, 更容易產(chǎn)生病原體厭惡(Milkowska et al., 2019)。進(jìn)一步研究證實(shí)了黃體期病原體厭惡敏感性與孕酮水平呈正相關(guān), 從而支持了“補(bǔ)償性預(yù)防假說” (?ela?niewicz et al., 2016)。但Jones等人(2018)采用大樣本、縱向研究卻未發(fā)現(xiàn)孕酮與病原體厭惡、道德厭惡、性厭惡的顯著相關(guān)。Fleischman和Fessler (2018)認(rèn)為Jones等人未發(fā)現(xiàn)孕激素與厭惡的關(guān)系, 可能是由于采用純文本測(cè)量厭惡不夠靈敏, 無法真實(shí)反應(yīng)厭惡敏感性的變化; 也可能孕酮不是導(dǎo)致厭惡敏感性增加的最直接因素, 而是同其他成分相互作用, 以一種更復(fù)雜的方式產(chǎn)生影響。

在厭惡面孔識(shí)別中, 孕激素具有顯著的調(diào)節(jié)作用。Conway等人(2007)發(fā)現(xiàn)孕酮水平與厭惡面孔的感知強(qiáng)度呈正相關(guān), 但受到面孔眼睛注視方向的調(diào)節(jié); 孕酮水平較高時(shí), 被試認(rèn)為斜視厭惡面孔更厭惡, 但孕酮水平不影響對(duì)直視厭惡面孔的感知。該作者認(rèn)為斜視暗示周圍環(huán)境存在傳染源, 而直視表示對(duì)感知者(被試)的厭惡, 因而認(rèn)為孕激素會(huì)增加女性對(duì)帶有疾病威脅的社會(huì)性線索的敏感性。該結(jié)論也得到了Derntl和Kryspin- Exner等人(2008)研究的支持, 他們發(fā)現(xiàn)高孕酮水平的黃體期女性更容易將負(fù)性表情面孔判定為厭惡。此外, 孕酮水平與厭惡面孔識(shí)別的反應(yīng)時(shí)也有正向關(guān)系(Hamstra et al., 2017; Kamboj et al., 2015)。孕激素增強(qiáng)感知強(qiáng)度和延長反應(yīng)時(shí), 可能表明了個(gè)體對(duì)厭惡面孔投入了更多的注意資源, 增強(qiáng)了對(duì)厭惡面孔的敏感性, 但降低了反應(yīng)速度。但準(zhǔn)確率上, 各研究結(jié)果差異很大, Maner和Miller (2014)發(fā)現(xiàn)黃體期孕酮水平增加提高了識(shí)別厭惡表情的準(zhǔn)確性。但Mikoli? (2016)卻發(fā)現(xiàn)黃體期厭惡表情沒有識(shí)別得更準(zhǔn)確。不同研究相互矛盾的結(jié)果, 可能是由實(shí)驗(yàn)任務(wù)和被試群體孕激素水平不同造成的, 未來研究應(yīng)注意任務(wù)難度的合理性和激素水平測(cè)量的精確性。

在道德厭惡上, 孕激素似乎沒有顯著影響, 多項(xiàng)研究測(cè)量各月經(jīng)周期孕酮水平和道德厭惡量表得分的關(guān)系, 均未發(fā)現(xiàn)二者存在相關(guān)(Jones et al., 2018; ?ela?niewicz et al., 2016)。這也從側(cè)面反映出相比于道德厭惡, 核心厭惡與孕激素的關(guān)系更為密切, 且具有更深遠(yuǎn)的進(jìn)化意義。但這些研究都采用量表測(cè)量道德厭惡, 可能限制了道德厭惡的范圍, 未來研究可嘗試實(shí)驗(yàn)操作的方法, 探究孕激素在道德厭惡中的作用。

4.2 孕激素影響厭惡加工的神經(jīng)機(jī)制

孕激素在神經(jīng)系統(tǒng)中具有重要作用, 包括參與神經(jīng)保護(hù), 調(diào)節(jié)神經(jīng)再生、星形膠質(zhì)細(xì)胞和突觸的可塑性等(Giatti et al., 2016)。其中, 孕酮具有高親脂性, 很容易通過血腦屏障在大腦中起作用。杏仁核(amygdala)是孕酮受體含量最高的腦區(qū)(Bixo et al., 1997), 也是情緒產(chǎn)生的核心腦區(qū), 在厭惡加工中顯著激活(Diano et al., 2017)。孕激素很可能通過影響杏仁核活動(dòng), 參與厭惡加工。

研究發(fā)現(xiàn), 杏仁核的興奮性會(huì)受到孕激素調(diào)節(jié)(Engman et al., 2018; Ossewaarde et al., 2010)。對(duì)健康女性月經(jīng)周期杏仁核活動(dòng)的功能性磁共振掃描發(fā)現(xiàn), 在觀看負(fù)性情緒面孔(恐懼和憤怒)時(shí), 高孕酮水平的黃體期杏仁核激活水平比卵泡期高(Gingnell et al., 2012)。卵泡期女性口服孕酮后, 選擇性增強(qiáng)了杏仁核的反應(yīng), 同時(shí)還調(diào)節(jié)了杏仁核與其他腦區(qū)之間的功能耦合(Van Wingen et al., 2008)。這些結(jié)果表明, 孕酮能增強(qiáng)杏仁核激活, 從而增強(qiáng)對(duì)負(fù)性刺激的反應(yīng)(Sundstr?m Poromaa & Gingnell, 2014), 這可能與孕酮增強(qiáng)核心厭惡刺激的感知強(qiáng)度有關(guān)。然而以上研究都沒有直接探討孕激素是否能增強(qiáng)杏仁核對(duì)厭惡刺激的反應(yīng), 但厭惡和恐懼同為回避性負(fù)性情緒, 可能具有共同的作用機(jī)制, 這還需通過實(shí)驗(yàn)進(jìn)一步確定在厭惡加工中孕激素對(duì)杏仁核的影響。

也有研究發(fā)現(xiàn)孕酮對(duì)杏仁核活動(dòng)的抑制作用。Derntl和Windischberger等人(2008)直接比較卵泡期(低雌二醇低孕酮)和黃體期(高雌二醇高孕酮)健康女性在情緒面孔識(shí)別時(shí)的杏仁核活動(dòng), 發(fā)現(xiàn)卵泡期厭惡表情識(shí)別準(zhǔn)確性更高, 且引發(fā)更大的杏仁核激活。該研究作者認(rèn)為低孕酮促進(jìn)杏仁核激活, 提高了對(duì)厭惡面孔的識(shí)別。不過該研究不能完全排除雌激素的作用, 且該研究采取橫斷研究, 每組被試量又太少, 可能對(duì)結(jié)果產(chǎn)生較大誤差。同時(shí), 也不能排除孕酮對(duì)杏仁核的抑制作用,因?yàn)閯e孕烷醇酮(allopregnanolone)及其他孕酮的神經(jīng)活性代謝物通常對(duì)γ-氨基丁酸受體(GABA-Rs)起正調(diào)節(jié)作用, 而GABA是大腦中最廣泛的抑制性神經(jīng)遞質(zhì)(Sundstr?m-Poromaa et al., 2020)。因此, 還需要更嚴(yán)格地控制其他激素水平, 探究孕激素與杏仁核活動(dòng)的關(guān)系, 進(jìn)一步確定孕激素?fù)p害厭惡表情準(zhǔn)確性是否與杏仁核抑制相關(guān)。

5 雌激素影響厭惡加工及其神經(jīng)機(jī)制

5.1 雌激素影響厭惡加工

5.1.1 動(dòng)物實(shí)驗(yàn)

雌激素(estrogen)已被證明參與調(diào)節(jié)嚙齒動(dòng)物的社會(huì)認(rèn)知、社會(huì)學(xué)習(xí), 以及對(duì)病原體/毒素的回避和厭惡情緒表達(dá), 這些行為主要是由嗅覺介導(dǎo)的(Choleris et al., 2012; Ervin et al., 2015)。例如, 相比于正常小鼠, 雌激素受體ERα和ERβ基因缺失的雌性小鼠辨別感染同伴氣味的能力受損, 對(duì)感染同伴表現(xiàn)出更少的回避和厭惡反應(yīng)(Choleris et al., 2009)。

此外, 雌激素在嚙齒動(dòng)物的厭惡學(xué)習(xí)中也具有重要作用。相比于雄性大鼠, 雌性大鼠條件性厭惡反應(yīng)更強(qiáng), 且在發(fā)情期條件性厭惡顯著增加, 這表明發(fā)情期雌激素增加可能增強(qiáng)了毒素誘導(dǎo)的惡心與新環(huán)境的聯(lián)系, 促進(jìn)小鼠條件性味覺厭惡習(xí)得(Cloutier et al., 2018; Lin et al., 2015)。這表明雌激素也可能在基于味覺的厭惡學(xué)習(xí)中起作用。

5.1.2 人體實(shí)驗(yàn)

在人類研究中, 目前還未發(fā)現(xiàn)雌激素對(duì)核心厭惡和道德厭惡加工的影響(Jones et al., 2018), 雌激素對(duì)厭惡加工的影響主要體現(xiàn)在表情識(shí)別上。研究發(fā)現(xiàn), 雌激素影響厭惡表情識(shí)別, 但似乎不同于雌激素對(duì)悲傷、憤怒、恐懼等負(fù)性表情的促進(jìn)作用(Guapo et al., 2009; Pearson & Lewis, 2005), 而是會(huì)損害厭惡表情識(shí)別的準(zhǔn)確性。雌二醇(estradiol)是人類最有效的內(nèi)源性雌激素(Gogos et al., 2014)。雌二醇水平較高的卵泡期, 女性識(shí)別厭惡面孔的錯(cuò)誤率明顯升高(Gasbarri et al., 2008)。Kamboj等人(2015)通過動(dòng)態(tài)面部表情識(shí)別任務(wù), 也發(fā)現(xiàn)月經(jīng)周期中雌二醇水平與厭惡表情識(shí)別的正確率呈負(fù)相關(guān)。也有研究發(fā)現(xiàn)雌激素不影響厭惡表情識(shí)別(Gasbarri et al., 2019; Pearson & Lewis, 2005), 但這兩項(xiàng)研究都沒有對(duì)被試的雌激素水平進(jìn)行確切測(cè)量, 不能保證所選不同月經(jīng)周期階段被試的雌激素水平是否存在顯著差異, 故不能明確得出雌激素與厭惡表情識(shí)別無關(guān)的結(jié)論。一項(xiàng)綜述研究提到卵泡期雌激素的增加有利于識(shí)別面部表情, 其目的是增加交配的機(jī)會(huì)(Osório et al., 2018), 但雌激素降低厭惡表情加工能力似乎不具有這樣的進(jìn)化適應(yīng)性, 未來研究需更嚴(yán)謹(jǐn)?shù)靥骄看萍に嘏c厭惡表情加工的關(guān)系, 以及這種關(guān)系背后的作用機(jī)制。

5.2 雌激素影響厭惡加工的神經(jīng)機(jī)制

在情緒加工相關(guān)的腦區(qū)(如扣帶回、杏仁核、海馬、下丘腦等)存在大量雌激素受體, 雌激素能增強(qiáng)這些腦區(qū)的興奮性突觸傳遞, 尤其能正向調(diào)節(jié)NMDA (N-甲基-D-天冬氨酸)受體功能(Lymer et al., 2018; Zang et al., 2020)。

研究發(fā)現(xiàn), 內(nèi)側(cè)杏仁核的雌激素能快速地促進(jìn)雌性小鼠的社會(huì)識(shí)別(Lymer et al., 2018)。厭惡情緒與社會(huì)識(shí)別高度相關(guān)(Kavaliers, Ossenkopp, et al., 2019), 雌激素可能通過影響杏仁核活動(dòng), 參與識(shí)別群體外不熟悉個(gè)體和被感染同伴, 產(chǎn)生厭惡情緒和回避行為, 未來可進(jìn)一步研究杏仁核是否介導(dǎo)雌激素影響厭惡加工。在厭惡學(xué)習(xí)中, Lin等人(2015)發(fā)現(xiàn)雌激素促進(jìn)小鼠條件性味覺厭惡習(xí)得, 其可能的作用機(jī)制是雌二醇使腦島?外側(cè)基底核之間的乙酰膽堿和/或谷氨酸能活動(dòng)增強(qiáng)。此外, Goldstein等人(2005)提出雌激素可能通過控制下丘腦?垂體?腎上腺回路中的皮層?皮質(zhì)下激活來減弱女性對(duì)負(fù)性情緒刺激的覺醒, 這也許是雌激素抑制厭惡表情識(shí)別能力的原因。

疼痛(pain)不僅能夠引起軀體上的痛, 還伴隨著情緒上的苦(厭惡)。痛刺激(如用刀刺傷皮膚)和核心厭惡刺激(如蚯蚓在皮膚上蠕動(dòng))共同激活扣帶回、左腦島、前額葉和右頂葉(Benuzzi et al., 2008)。前扣帶回(ACC)是大腦中調(diào)節(jié)情感性疼痛的重要區(qū)域(Wu et al., 2019), 抑制ACC的過度活躍能減少嚙齒類動(dòng)物對(duì)疼痛的厭惡(Zhou et al., 2018)。進(jìn)一步研究發(fā)現(xiàn), 大鼠ACC中的腦源性雌激素是痛厭惡形成的關(guān)鍵(Zang et al., 2020), 其作用機(jī)制是ACC局部合成的雌二醇通過激活NMDA受體, 快速增強(qiáng)ACC神經(jīng)元興奮性突觸傳遞和突觸可塑性(Xiao et al., 2013)。雌激素或許也能通過影響ACC中神經(jīng)元的結(jié)構(gòu)與功能, 對(duì)更廣泛的厭惡情緒產(chǎn)生影響。

6 總結(jié)與展望

催產(chǎn)素、孕激素和雌激素不同程度地影響厭惡加工, 各激素影響厭惡加工的異同如表1所示。但目前的研究結(jié)果還存在許多矛盾之處, 例如?ela?niewicz等人(2016)發(fā)現(xiàn)孕酮水平與厭惡敏感度呈正相關(guān), Kamboj等人(2015)發(fā)現(xiàn)高雌二醇能提高厭惡表情識(shí)別速度, 但Jones等人(2018)的研究結(jié)果并不支持上述研究。實(shí)驗(yàn)結(jié)果的不一致可能是由激素測(cè)量方式、厭惡評(píng)價(jià)方法以及實(shí)驗(yàn)任務(wù)不同導(dǎo)致的。此外, 目前大多研究還停留于描述現(xiàn)象和相關(guān)研究階段, 對(duì)其內(nèi)在作用機(jī)制知之甚少。未來研究應(yīng)當(dāng)注意激素測(cè)量準(zhǔn)確性, 在月經(jīng)周期中開展縱向追蹤研究, 來提高實(shí)驗(yàn)的內(nèi)部效度; 同時(shí)測(cè)量情緒反應(yīng)指標(biāo)時(shí)應(yīng)避免“天花板效應(yīng)”或“地板效應(yīng)”干擾實(shí)驗(yàn)結(jié)果。在此基礎(chǔ)上, 重點(diǎn)關(guān)注以下幾個(gè)方面。

6.1 各激素對(duì)不同感覺通道厭惡加工的影響

在動(dòng)物模型中, 以往主要探究了催產(chǎn)素、孕激素和雌激素對(duì)基于嗅覺的病原體厭惡感知(Choleris et al., 2009; Kavaliers, Colwell, et al., 2019)和基于味覺的條件性厭惡表達(dá)(Boulet et al., 2016; Cloutier et al., 2018)的影響, 以及雌激素對(duì)基于觸覺的痛厭惡的調(diào)節(jié)作用(Zang et al., 2020)。在人類被試中, 研究更多的局限于三種激素對(duì)視覺厭惡刺激加工的影響, 尤其是對(duì)厭惡面孔識(shí)別的影響(Hamstra et al., 2017; Kamboj et al., 2015; Leppanen et al., 2017)。厭惡情緒可以通過味、嗅、視、聽、觸多個(gè)感覺通道觸發(fā)。研究發(fā)現(xiàn), 以上三種激素在嗅覺、味覺、視覺、聽覺和軀體感覺中具有不同程度的調(diào)節(jié)作用(Grinevich & Stoop, 2018; Shuster et al., 2019; Tomás et al., 2019)。由此, 不同激素可能對(duì)不同感覺通道的信息加工有不同影響, 未來研究可進(jìn)一步探究這三種激素對(duì)不同感覺通道厭惡刺激加工的作用。

6.2 各激素對(duì)不同性別個(gè)體厭惡加工的影響

從嚙齒動(dòng)物、非人類靈長類動(dòng)物到人類, 女(雌)性在厭惡加工上具有跨物種一致的優(yōu)勢(shì), 其厭惡敏感性更高, 厭惡線索識(shí)別更好, 厭惡體驗(yàn)更強(qiáng)(Al-Shawaf et al., 2018; Cloutier et al., 2018; Poirotte et al., 2019)。這種性別差異可能部分源于兩性激素的差異, 同時(shí)激素對(duì)厭惡加工的影響很可能也受到性別的調(diào)節(jié)。例如, Declerck等人(2014)發(fā)現(xiàn)OT降低了女性厭惡感, 但對(duì)男性沒有影響。在神經(jīng)基礎(chǔ)上, OT增強(qiáng)女性杏仁核對(duì)威脅刺激的激活, 在男性中卻起相反作用(Lieberz et al., 2020)。考慮到雌激素和孕激素給藥的副作用, 目前對(duì)人類的研究主要考察月經(jīng)周期中內(nèi)源性孕/雌激素的變化對(duì)厭惡加工的影響, 實(shí)驗(yàn)對(duì)象均選用女性被試。還尚未明確這兩種激素對(duì)厭惡加工的影響是否有性別依賴性。未來可結(jié)合動(dòng)物研究, 通過外源性激素給藥, 探討激素影響厭惡加工的性別調(diào)節(jié)作用, 并在此基礎(chǔ)上重點(diǎn)關(guān)注產(chǎn)生這種性別差異的作用機(jī)制。

表1 三種激素對(duì)厭惡加工影響的異同

6.3 結(jié)合多種技術(shù), 探究各激素影響厭惡的神經(jīng)內(nèi)分泌機(jī)制

通過前文綜述, 我們發(fā)現(xiàn)催產(chǎn)素影響腦島、前扣帶回、杏仁核、梨狀皮層、殼核、額中回等多個(gè)腦區(qū)活動(dòng)從而參與厭惡情緒加工; 孕激素可能主要通過調(diào)節(jié)杏仁核活動(dòng)及其與其他腦區(qū)之間的功能耦合參與厭惡識(shí)別; 但雌激素調(diào)節(jié)厭惡加工的神經(jīng)機(jī)制還沒有太多直接證據(jù)。未來研究可以借助事件相關(guān)電位(ERPs)、功能性磁共振成像技術(shù)(fMRI)和功能性近紅外光譜技術(shù)(fNIRS)等技術(shù), 探索三種激素調(diào)節(jié)厭惡加工的神經(jīng)機(jī)制。同時(shí)通過動(dòng)物行為學(xué), 結(jié)合免疫組織化學(xué)、活細(xì)胞檢測(cè)等實(shí)驗(yàn)方法, 探索三種激素對(duì)5-HT、GABA、NMDA和乙酰膽堿等神經(jīng)遞質(zhì)系統(tǒng)的調(diào)節(jié), 進(jìn)一步明確它們調(diào)節(jié)厭惡加工的神經(jīng)內(nèi)分泌機(jī)制。

雷怡, 孫曉瑩, 竇皓然. (2019). 恐懼與厭惡情緒圖片系統(tǒng)的編制: 基于兩種情緒的區(qū)分.,(3), 521–528.

Ackerman, J. M., Hill, S. E., & Murray, D. R. (2018). The behavioral immune system: Current concerns and future directions.,(2), e12371.

Allsop, S. A., Wichmann, R., Mills, F., Burgos-Robles, A., Chang, C.-J., Felix-Ortiz, A. C., … Tye, K. M. (2018). Corticoamygdala transfer of socially derived information gates observational learning.,(6), 1329–1342.

Al-Shawaf, L., Lewis, D. M., & Buss, D. M. (2018). Sex differences in disgust: Why are women more easily disgusted than men?,(2), 149–160.

Amir, N., Klumpp, H., Elias, J., Bedwell, J. S., Yanasak, N., & Miller, L. S. (2005). Increased activation of the anterior cingulate cortex during processing of disgust faces in individuals with social phobia.,(9), 975–981.

Behringer, D. C., Butler, M. J., & Shields, J. D. (2006). Avoidance of disease by social lobsters.,(7092), 421–421.

Benuzzi, F., Lui, F., Duzzi, D., Nichelli, P. F., & Porro, C. A. (2008). Does it look painful or disgusting? Ask your parietal and cingulate cortex.,(4), 923– 931.

Bernhard, R. M., Chaponis, J., Siburian, R., Gallagher, P., Ransohoff, K., Wikler, D., … Greene, J. D. (2016). Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment.,(12), 1872–1881.

Berret, E., Kintscher, M., Palchaudhuri, S., Tang, W., Osypenko, D., Kochubey, O., & Schneggenburger, R. (2019). Insular cortex processes aversive somatosensory information and is crucial for threat learning.,(6443), eaaw0474.

Bia?ek, M., Muda, R., Fugelsang, J., & Friedman, O. (2021). Disgust and moral judgment: Distinguishing between elicitors and feelings matters.,(3), 304–313.

Bixo, M., Andersson, A., Winblad, B., Purdy, R. H., & B?ckstr?m, T. (1997). Progesterone, 5α-pregnane-3, 20-dione and 3α-hydroxy-5α-pregnane-20-one in specific regions of the human female brain in different endocrine states.,(1-2), 173–178.

Boccia, M. L., Petrusz, P., Suzuki, K., Marson, L., & Pedersen,C. A. (2013). Immunohistochemical localization of oxytocin receptors in human brain.,, 155–164.

Boulet, N. P., Cloutier, C. J., Ossenkopp, K.-P., & Kavaliers, M. (2016). Oxytocin, social factors, and the expression of conditioned disgust (anticipatory nausea) in male rats.,(8), 718–725.

Bressan, P., & Kramer, P. (2021). Progesterone does raise disgust., 104937.

Cardoso, C., Ellenbogen, M. A., & Linnen, A.-M. (2014). The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).,(1), 43–50.

Caruana, F., Jezzini, A., Sbriscia-Fioretti, B., Rizzolatti, G., & Gallese, V. (2011). Emotional and social behaviors elicited by electrical stimulation of the insula in the macaque monkey.,(3), 195–199.

Cepon-Robins, T. J., Blackwell, A. D., Gildner, T. E., Liebert, M. A., Urlacher, S. S., Madimenos, F. C., … Sugiyama, L. S. (2021). Pathogen disgust sensitivity protects against infection in a high pathogen environment.,(8), e2018552118.

Chambers, K. C. (1980). Progesterone, estradiol, testosterone and dihydrotestosterone: Effects on rate of extinction of a conditioned taste aversion in rats.,(6), 1061–1065.

Chapman, H. A., Kim, D. A., Susskind, J. M., & Anderson, A. K. (2009). In bad taste: Evidence for the oral origins of moral disgust.,(5918), 1222–1226.

Choe, H. K., Reed, M. D., Benavidez, N., Montgomery, D., Soares, N., Yim, Y. S., & Choi, G. B. (2015). Oxytocin mediates entrainment of sensory stimuli to social cues of opposing valence.,(1), 152–163.

Choleris, E., Clipperton-Allen, A. E., Phan, A., & Kavaliers, M. (2009). Neuroendocrinology of social information processing in rats and mice.,(4), 442–459.

Choleris, E., Clipperton-Allen, A. E., Phan, A., Valsecchi, P., & Kavaliers, M. (2012). Estrogenic involvement in social learning, social recognition and pathogen avoidance.,(2), 140–159.

Cloutier, C. J., Zevy, D. L., Kavaliers, M., & Ossenkopp, K.-P. (2018). Conditioned disgust in rats (anticipatory nausea) to a context paired with the effects of the toxin LiCl: Influence of sex and the estrous cycle.,, 51–57.

Conway, C. A., Jones, B. C., DeBruine, L. M., Welling, L. L. M., Law Smith, M. J., Perrett, D. I., … Al-Dujaili, E. A. S. (2007). Salience of emotional displays of danger and contagion in faces is enhanced when progesterone levels are raised.,(2), 202–206.

Corradi-Dell’Acqua, C., Tusche, A., Vuilleumier, P., & Singer, T. (2016). Cross-modal representations of first- hand and vicarious pain, disgust and fairness in insular and cingulate cortex.,(1), 1–12.

Darwin, C., & Prodger, P. (1998).. New York: Oxford University Press.

Declerck, C. H., Lambert, B., & Boone, C. (2014). Sexual dimorphism in oxytocin responses to health perception and disgust, with implications for theories on pathogen detection.,(5), 521–526.

Derntl, B., Kryspin-Exner, I., Fernbach, E., Moser, E., & Habel, U. (2008). Emotion recognition accuracy in healthy young females is associated with cycle phase.,(1), 90–95.

Derntl, B., Windischberger, C., Robinson, S., Lamplmayr, E., Kryspin-Exner, I., Gur, R. C., … Habel, U. (2008). Facial emotion recognition and amygdala activation are associated with menstrual cycle phase.,(8), 1031–1040.

Diano, M., Tamietto, M., Celeghin, A., Weiskrantz, L., Tatu, M.-K., Bagnis, A., … Costa, T. (2017). Dynamic changes in amygdala psychophysiological connectivity reveal distinct neural networks for facial expressions of basic emotions.,, 45260.

Dolensek, N., Gehrlach, D. A., Klein, A. S., & Gogolla, N. (2020). Facial expressions of emotion states and their neuronal correlates in mice.,(6486), 89–94.

Duque-Wilckens, N., Steinman, M. Q., Busnelli, M., Chini, B., Yokoyama, S., Pham, M., … Trainor, B. C. (2018). Oxytocin receptors in the anteromedial bed nucleus of the stria terminalis promote stress-induced social avoidance in female California mice.,(3), 203–213.

Engman, J., Poromaa, I. S., Moby, L., Wikstr?m, J., Fredrikson, M., & Gingnell, M. (2018). Hormonal cycle and contraceptive effects on amygdala and salience resting-state networks in women with previous affective side effects on the pill.,(3), 555–563.

Ervin, K. S. J., Lymer, J. M., Matta, R., Clipperton-Allen, A. E., Kavaliers, M., & Choleris, E. (2015). Estrogen involvement in social behavior in rodents: Rapid and long-term actions.,, 53–76.

Fessler, D. M. T., Eng, S. J., & Navarrete, C. D. (2005). Elevated disgust sensitivity in the first trimester of pregnancy: Evidence supporting the compensatory prophylaxis hypothesis.,(4), 344–351.

Fleischman, D. S., & Fessler, D. M. T. (2018). Response to “hormonal correlates of pathogen disgust: Testing the compensatory prophylaxis hypothesis”.,(4), 468–469.

Gasbarri, A., D'Amico, M., Arnone, B., Iorio, C., Pacitti, F., Ciotti, S., Iorio, P., & Pompili, A. (2019). Electrophysiological and behavioral indices of the role of estrogens on memory processes for emotional faces in healthy young women.,, 234.

Gasbarri, A., Pompili, A., d’Onofrio, A., Cifariello, A., Tavares, M. C., & Tomaz, C. (2008). Working memory for emotional facial expressions: Role of the estrogen in young women.,(7), 964–972.

Giatti, S., Melcangi, R. C., & Pesaresi, M. (2016). The other side of progestins: effects in the brain.,(2), R109–R126.

Gingnell, M., Morell, A., Bannbers, E., Wikstr?m, J., & Sundstr?m Poromaa, I. (2012). Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder.,(4), 400– 406.

Gogos, A., Wu, Y. C., Williams, A. S., & Byrne, L. K. (2014). The effects of ethinylestradiol and progestins (“the pill”) on cognitive function in pre-menopausal women.,(12), 2288–2300.

Goldstein, J. M., Jerram, M., Poldrack, R., Ahern, T., Kennedy, D. N., Seidman, L. J., & Makris, N. (2005). Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging.,(40), 9309–9316.

Gorka, S. M., Fitzgerald, D. A., Labuschagne, I., Hosanagar, A., Wood, A. G., Nathan, P. J., & Phan, K. L. (2015). Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder.,(2), 278–286.

Grinevich, V., & Stoop, R. (2018). Interplay between oxytocin and sensory systems in the orchestration of socio-emotional behaviors.,(5), 887–904.

Guapo, V. G., Graeff, F. G., Zani, A. C. T., Labate, C. M., dos Reis, R. M., & Del-Ben, C. M. (2009). Effects of sex hormonal levels and phases of the menstrual cycle in the processing of emotional faces.,(7), 1087–1094.

Hamstra, D. A., de Kloet, E. R., Quataert, I., Jansen, M., & van der Does, W. (2017). Mineralocorticoid receptor haplotype, estradiol, progesterone and emotional information processing.,, 162–173.

Jones, B. C., Hahn, A. C., Fisher, C. I., Wang, H. Y., Kandrik, M., Lee, A. J., … DeBruine, L. M. (2018). Hormonal correlates of pathogen disgust: testing the compensatory prophylaxis hypothesis.,(2), 166–169.

Kamboj, S. K., Krol, K. M., & Curran, H. V. (2015). A specific association between facial disgust recognition and estradiol levels in naturally cycling women.,(4), e0122311.

Kavaliers, M., Bishnoi, I. R., Ossenkopp, K.-P., & Choleris, E. (2021a). Differential effects of progesterone on social recognition and the avoidance of pathogen threat by female mice.,, 104873.

Kavaliers, M., Bishnoi, I. R., Ossenkopp, K.-P., & Choleris, E. (2021b). Progesterone and disgust: A response to" progesterone does raise disgust"., 104936.

Kavaliers, M., & Choleris, E. (2011). Sociality, Pathogen Avoidance, and the Neuropeptides Oxytocin and Arginine Vasopressin.,(11), 1367–1374.

Kavaliers, M., Choleris, E., ?gmo, A., & Pfaff, D. W. (2004). Olfactory-mediated parasite recognition and avoidance: linking genes to behavior.,(3), 272–283.

Kavaliers, M., Colwell, D. D., Wah, D. T. O., Bishnoi, I. R., Ossenkopp, K.-P., & Choleris, E. (2019). Conspecific infection threat rapidly biases the social responses of female mice: involvement of oxytocin.,, 67–75.

Kavaliers, M., Ossenkopp, K. P., & Choleris, E. (2019). Social neuroscience of disgust.,(1), e12508.

Kavaliers, M., Ossenkopp, K.-P., & Choleris, E. (2020). Pathogens, odors, and disgust in rodents.,, 281–293.

Khalil, R. B., Bou-Orm, I. R., Tabet, Y., Souaiby, L., & Azouri, H. (2020). Disgust and fear: common emotions between eating and phobic disorders.,(1), 79–86.

Kiesecker, J. M., Skelly, D. K., Beard, K. H., & Preisser, E. (1999). Behavioral reduction of infection risk.,(16), 9165–9168.

Kim, Y.-R., Kim, C.-H., Park, J. H., Pyo, J. M., & Treasure, J. (2014). The impact of intranasal oxytocin on attention to social emotional stimuli in patients with anorexia nervosa: A double blind within-subject cross-over experiment.,(6), e90721.

Knowles, K. A., Jessup, S. C., & Olatunji, B. O. (2018). Disgust in anxiety and obsessive-compulsive disorders: recent findings and future directions.,(9), 68.

Labuschagne, I., Poudel, G., Kordsachia, C., Wu, Q., Thomson, H., Georgiou-Karistianis, N., & Stout, J. C. (2018). Oxytocin selectively modulates brain processing of disgust in Huntington's disease gene carriers.,, 11–16.

Leppanen, J., Ng, K. W., Tchanturia, K., & Treasure, J. (2017). Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.,, 125–144.

Lieberz, J., Scheele, D., Spengler, F. B., Matheisen, T., Schneider, L., Stoffel-Wagner, B., … Hurlemann, R. (2020). Kinetics of oxytocin effects on amygdala and striatal reactivity vary between women and men.,(7), 1134–1140.

Limebeer, C. L., Rock, E. M., Sharkey, K. A., & Parker, L. A. (2018). Nausea-induced 5-HT release in the interoceptive insular cortex and regulation by monoacylglycerol lipase (MAGL) inhibition and cannabidiol.(4), ENEURO.0256–0218.2018.

Lin, S.-F., Tsai, Y.-F., Tai, M.-Y., & Yeh, K.-Y. (2015). Estradiol enhances the acquisition of lithium chloride- induced conditioned taste aversion in castrated male rats.,(9), 1–8.

Luo, L. Z., Becker, B., Geng, Y. Y., Zhao, Z. Y., Gao, S., Zhao, W. H., … Kendrick, K. M. (2017). Sex-dependent neural effect of oxytocin during subliminal processing of negative emotion faces.,, 127–137.

Lymer, J. M., Sheppard, P. A. S., Kuun, T., Blackman, A., Jani, N., Mahbub, S., & Choleris, E. (2018). Estrogens and their receptors in the medial amygdala rapidly facilitate social recognition in female mice.,, 30–38.

Maner, J. K., & Miller, S. L. (2014). Hormones and social monitoring: Menstrual cycle shifts in progesterone underlie women's sensitivity to social information.,(1), 9–16.

Mazzola, L., Mauguière, F., & Isnard, J. (2017). Electrical stimulations of the human insula: their contribution to the ictal semiology of insular seizures.,(4), 307–314.

Mikoli?, A. (2016). Disgust and facial expression recognition across the menstrual cycle.,, 31–60.

Milkowska, K., Galbarczyk, A., & Jasienska, G. (2019). Disgust sensitivity in relation to menstrual cycle phase in women with and without an infection.,(3), e23233.

Molho, C., Tybur, J. M., Güler, E., Balliet, D., & Hofmann, W. (2017). Disgust and anger relate to different aggressive responses to moral violations.,(5), 609–619.

Moran, T., Bornstein, O., & Eyal, T. (2019). The level of construal involved in the elicitation of core versus moral disgust.,(2), 391–404.

Mottolese, R., Redouté, J., Costes, N., Le Bars, D., & Sirigu, A. (2014). Switching brain serotonin with oxytocin.,(23), 8637–8642.

Murray, D. R., Prokosch, M. L., & Airington, Z. (2019). PsychoBehavioroimmunology: Connecting the Behavioral Immune System to Its Physiological Foundations.,, 200.

Oaten, M., Stevenson, R. J., & Case, T. I. (2009). Disgust as a disease-avoidance mechanism.,(2), 303–321.

Olatunji, B. O., Moretz, M. W., McKay, D., Bjorklund, F., de Jong, P. J., Haidt, J., ... Schienle, A. (2009). Confirming the three-factor structure of the disgust scale-revised in eight countries.,(2), 234–255.

Olszewski, P. K., Waas, J. R., Brooks, L. L., Herisson, F., & Levine, A. S. (2013). Oxytocin receptor blockade reduces acquisition but not retrieval of taste aversion and blunts responsiveness of amygdala neurons to an aversive stimulus.,, 36–41.

O'Shea, K. J., DeBruine, L. M., & Jones, B. C. (2019). Further evidence for associations between short-term mating strategy and sexual disgust.,, 333–335.

Osório, F. L., de Paula Cassis, J. M., Machado de Sousa, J. P., Poli-Neto, O., & Martín-Santos, R. (2018). Sex hormones and processing of facial expressions of emotion: A systematic literature review.,, 529.

Ossewaarde, L., Hermans, E. J., van Wingen, G. A., Kooijman, S. C., Johansson, I.-M., B?ckstr?m, T., & Fernández, G. (2010). Neural mechanisms underlying changes in stress-sensitivity across the menstrual cycle.,(1), 47–55.

Pearson, R., & Lewis, M. B. (2005). Fear recognition across the menstrual cycle.,(3), 267–271.

Pilarczyk, J., Schwertner, E., Wo?oszyn, K., & Kuniecki, M. (2019). Phase of the menstrual cycle affects engagement of attention with emotional images.,, 25–32.

Pisansky, M. T., Hanson, L. R., Gottesman, I. I., & Gewirtz, J. C. (2017). Oxytocin enhances observational fear in mice.,(1), 2102.

Poirotte, C., Sarabian, C., Ngoubangoye, B., MacIntosh, A. J. J., & Charpentier, M. (2019). Faecal avoidance differs between the sexes but not with nematode infection risk in mandrills.,, 97–106.

Rogers-Carter, M. M., Varela, J. A., Gribbons, K. B., Pierce, A. F., McGoey, M. T., Ritchey, M., & Christianson, J. P. (2018). Insular cortex mediates approach and avoidance responses to social affective stimuli.,(3), 404–414.

Rozin, P., & Fallon, A. E. (1987). A perspective on disgust.,(1), 23–41.

Rozin, P., Haidt, J., & Fincher, K. (2009). From oral to moral.,(5918), 1179–1180.

Rozin, P., Haidt, J., & McCauley, C. R. (2016). Disgust. In L. F. Barrett, M. Lewis, & J. M. Haviland-Jones (Eds.),(pp. 815–834). Guilford Press.

Scheele, D., Striepens, N., Kendrick, K. M., Schwering, C., Noelle, J., Wille, A., … Hurlemann, R. (2014). Opposing effects of oxytocin on moral judgment in males and females.,(12), 6067–6076.

Schier, L. A., Hyde, K. M., & Spector, A. C. (2019). Conditioned taste aversion versus avoidance: A re-examination of the separate processes hypothesis.,(6), e0217458.

Schr?der, A., van Wingen, G., Eijsker, N., San Giorgi, R., Vulink, N. C., Turbyne, C., & Denys, D. (2019). Misophonia is associated with altered brain activity in the auditory cortex and salience network.,(1), 7542.

Shah, N. M., Imami, N., & Johnson, M. R. (2018). Progesterone Modulation of Pregnancy-Related Immune Responses.,, 1293.

Shook, N. J., Oosterhoff, B., Terrizzi Jr, J. A., & Brady, K. M. (2017). “Dirty politics”: The role of disgust sensitivity in voting.,(3), 284–297.

Shook, N. J., Sevi, B., Lee, J., Oosterhoff, B., & Fitzgerald, H. N. (2020). Disease avoidance in the time of COVID-19: The behavioral immune system is associated with concern and preventative health behaviors.,(8), e0238015.

Shuster, B. Z., Depireux, D. A., Mong, J. A., & Hertzano, R. (2019). Sex differences in hearing: Probing the role of estrogen signaling.,(6), 3656–3663.

Steinberg, E. E., Gore, F., Heifets, B. D., Taylor, M. D., Norville, Z. C., Beier, K. T., … Malenka, R. C. (2020). Amygdala-midbrain connections modulate appetitive and aversive learning.,(6), 1026–1043.

Stevenson, R. J., Case, T. I., Oaten, M. J., Stafford, L., & Saluja, S. (2019). A proximal perspective on disgust.,(3), 209–225.

Sundstr?m-Poromaa, I., Comasco, E., Sumner, R., & Luders, E. (2020). Progesterone-friend or foe?,, 100856.

Sundstr?m Poromaa, I., & Gingnell, M. (2014). Menstrual cycle influence on cognitive function and emotion processing- from a reproductive perspective.,, 380.

Theodoridou, A., Penton-Voak, I. S., & Rowe, A. C. (2013). A direct examination of the effect of intranasal administration of oxytocin on approach-avoidance motor responses to emotional stimuli.,(2), e58113.

Tomás, J., Santos, C. R. A., Duarte, A. C., Maltez, M., Quintela, T., Lemos, M. C., & Gon?alves, I. (2019). Bitter taste signaling mediated by Tas2r144 is down-regulated by 17β-estradiol and progesterone in the rat choroid plexus.,, 110521.

Tuerke, K. J., Limebeer, C. L., Fletcher, P. J., & Parker, L. A. (2012). Double dissociation between regulation of conditioned disgust and taste avoidance by serotonin availability at the 5-HT3receptor in the posterior and anterior insular cortex.,(40), 13709–13717.

Tybur, J. M., Lieberman, D., Kurzban, R., & DeScioli, P. (2013). Disgust: Evolved function and structure.,(1), 65–84.

van Wingen, G. A., van Broekhoven, F., Verkes, R. J., Petersson, K. M., B?ckstr?m, T., Buitelaar, J. K., & Fernández, G. (2008). Progesterone selectively increases amygdala reactivity in women.,(3), 325–333.

Verbalis, J. G., McHale, C. M., Gardiner, T. W., & Stricker, E. M. (1986). Oxytocin and vasopressin secretion in response to stimuli producing learned taste aversions in rats.,(4), 466–475.

Wang, D. Y., Yan, X. Y., Li, M., & Ma, Y. N. (2017). Neural substrates underlying the effects of oxytocin: a quantitative meta-analysis of pharmaco-imaging studies.,(10), 1565–1573.

Wang, T. Y., Tang, Q. T., Wu, X., & Chen, X. (2020). Attachment anxiety moderates the effect of oxytocin on negative emotion recognition: Evidence from eye-movementdata.,, 173015.

Weinstein, S. B., Buck, J. C., & Young, H. S. (2018). A landscape of disgust.,(6381), 1213–1214.

Wicker, B., Keysers, C., Plailly, J., Royet, J.-P., Gallese, V., & Rizzolatti, G. (2003). Both of Us Disgusted in My Insula: The Common Neural Basis of Seeing and Feeling Disgust.,(3), 655–664.

Wu, X.-B., He, L.-N., Jiang, B.-C., Wang, X., Lu, Y., & Gao, Y.-J. (2019). Increased CXCL13 and CXCR5 in anterior cingulate cortex contributes to neuropathic pain-related conditioned place aversion.,(4), 613–623.

Xiao, X., Yang, Y., Zhang, Y., Zhang, X.-M., Zhao, Z.-Q., & Zhang, Y.-Q. (2013). Estrogen in the anterior cingulate cortex contributes to pain-related aversion.,(9), 2190–2203.

Yao, S. X., Becker, B., Zhao, W. H., Zhao, Z. Y., Kou, J., Ma, X. L., … Kendrick, K. M. (2018). Oxytocin modulates attention switching between interoceptive signals and external social cues.,(2), 294–301.

Zang, K.-K., Xiao, X., Chen, L.-Q., Yang, Y., Cao, Q.-L., Tang, Y.-L., … Zhang, Y.-Q. (2020). Distinct function of estrogen receptors in the rodent anterior cingulate cortex in pain-related aversion.,(1), 165–184.

?ela?niewicz, A., Borkowska, B., Nowak, J., & Paw?owski, B. (2016). The progesterone level, leukocyte count and disgust sensitivity across the menstrual cycle.,, 60–65.

Zhou, H. C., Zhang, Q. S., Martinez, E., Dale, J., Hu, S., Zhang, E., … Wang, J. (2018). Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex.,(1), 3751.

The influence of oxytocin, progesterone and estrogen on disgust and its neurophysiological mechanism

ZHANG Xia, LEI Yi, WANG Fushun

(Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu 610066, China)

Disgust is an important basic emotion for human beings and animals, and it derives from distasteful oral responses to bitter (toxic) tastants, often accompanied with nausea and vomiting and a strong desire to stay away from the induced stimulus, and it has the function of avoiding potential disease threats. A large number of studies have shown that oxytocin, progesterone, and estrogens can affect perception, generation and expression of core disgust, as well as learning conditioned disgust and recognizing facial expression in varying degrees. These three hormones mainly affect the processing of disgust by modulating neurotransmitter receptors including serotonin, γ-aminobutyric acid, acetylcholine, and glutamic acid receptors, and thus affecting the activities of amygdala, insula, anterior cingulate gyrus, putamen, piriform cortex, and middle frontal gyrus. Future studies should explore the effects of these hormones on disgust in different sensory channels and also consider their moderating roles in different genders by accurately measuring hormone levels and controlling the task difficulties. In addition, researchers can combine neuroimaging technologies with behavioral studies to clarify the neuroendocrine mechanism of these hormones affecting disgust processing.

disgust, oxytocin, progesterone, estrogen, neurophysiological mechanism

B845

2021-01-05

* 教育部人文社科基金項(xiàng)目(19YJAZH083)。

王福順，E-mail: 13814541138@163.com