本文關(guān)鍵詞：自然發(fā)生的棕色田鼠不同水平的社會(huì)性形成和調(diào)節(jié)的神經(jīng)內(nèi)分泌機(jī)制　出處：《陜西師范大學(xué)》2016年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 棕色田鼠 社會(huì)性 加壓素系統(tǒng) 催產(chǎn)素系統(tǒng) 多巴胺系統(tǒng)

【摘要】：健康的社會(huì)交往和穩(wěn)定的社會(huì)聯(lián)系能力的減弱是許多精神疾病如抑郁癥,成癮,精神分裂癥和自閉癥等普遍的癥狀之一。理解正常社會(huì)聯(lián)系發(fā)育、形成的神經(jīng)生物機(jī)制和遺傳機(jī)制對(duì)理解上述這些精神疾病非常重要,也可為藥理干預(yù)和治療這些疾病提供可能的靶標(biāo)。社會(huì)聯(lián)系在生命活動(dòng)中普遍存在,它可以影響社會(huì)、心理、生理和行為機(jī)能。關(guān)于社會(huì)聯(lián)系的發(fā)育形成機(jī)制目前還不清楚,但是社會(huì)聯(lián)系涉及一系列復(fù)雜的過程,包括通過感覺發(fā)現(xiàn)同伴、識(shí)別熟悉的個(gè)體以及產(chǎn)生接近或接觸的動(dòng)機(jī)。此外,必須抑制如厭惡或攻擊等其他不利于社會(huì)聯(lián)系的行為。許多關(guān)于動(dòng)物和人類的研究已經(jīng)發(fā)現(xiàn)加壓素、催產(chǎn)素和多巴胺可以調(diào)節(jié)復(fù)雜的社會(huì)聯(lián)系。然而,這其中大多數(shù)的報(bào)道都集中在研究加壓素、催產(chǎn)素和多巴胺與和繁殖相關(guān)的社會(huì)聯(lián)系上,比如關(guān)于加壓素、催產(chǎn)素和多巴胺對(duì)親本行為和配偶聯(lián)系的調(diào)節(jié)。但是關(guān)于加壓素、催產(chǎn)素和多巴胺與非繁殖目的的社會(huì)聯(lián)系的研究報(bào)道還很有限。而且,生命早期社會(huì)經(jīng)歷的改變可以對(duì)幼崽腦和行為產(chǎn)生長(zhǎng)期的影響。早期社會(huì)環(huán)境的改變可以引起加壓素、催產(chǎn)素和多巴胺系統(tǒng)的改變,從而產(chǎn)生生理功能的系統(tǒng)性變化,這種變化是通過與繁殖有關(guān)的社會(huì)行為如親本行為和配偶聯(lián)系的變化體現(xiàn)的。但是早期社會(huì)環(huán)境的改變對(duì)非繁殖目的的社會(huì)聯(lián)系以及與之相關(guān)的神經(jīng)內(nèi)分泌機(jī)制的長(zhǎng)期影響仍然不清楚。另外,想全面的解釋中樞加壓素、催產(chǎn)素和多巴胺對(duì)社會(huì)聯(lián)系的所有影響是很困難的,因?yàn)檫@些神經(jīng)遞質(zhì)或調(diào)質(zhì)常常具有物種和/或性R%特異性,而且它們對(duì)社會(huì)聯(lián)系的影響在不同腦區(qū)是不同的。已經(jīng)有大量的證據(jù)表明在中樞神經(jīng)系統(tǒng)的特異位點(diǎn)注射加壓素、催產(chǎn)素和多巴胺可以對(duì)與繁殖有關(guān)的社會(huì)聯(lián)系產(chǎn)生顯著的影響。研究也表明具有加壓素、催產(chǎn)素和多巴胺受體的腦區(qū)比如伏核、杏仁內(nèi)側(cè)核等也調(diào)節(jié)著與社會(huì)聯(lián)系相關(guān)的行為。那么加壓素、催產(chǎn)素和多巴胺系統(tǒng)到底和動(dòng)物的社會(huì)性有什么聯(lián)系?早期的發(fā)育環(huán)境是否可通過改變加壓素、催產(chǎn)素和多巴胺系統(tǒng)進(jìn)而影響成年后的社會(huì)行為?這三個(gè)系統(tǒng)到底通過哪些腦區(qū)發(fā)揮作用?本研究以具有復(fù)雜社會(huì)性的單配制棕色田鼠為動(dòng)物模型,探討社會(huì)性形成和調(diào)節(jié)的神經(jīng)內(nèi)分泌機(jī)制,本研究有三個(gè)目的,首先,比較自然發(fā)生的不同社會(huì)性水平的棕色田鼠,其腦內(nèi)加壓素、催產(chǎn)素和多巴胺系統(tǒng)參數(shù)的表達(dá)是否存在差異;第二,棕色田鼠自然發(fā)生的不同水平的親本投資是否對(duì)社會(huì)性和加壓素、催產(chǎn)素和多巴胺系統(tǒng)的水平產(chǎn)生影響。第二,以棕色田鼠為模型觀察催產(chǎn)素能否在伏核對(duì)個(gè)體的社會(huì)行為起到促進(jìn)作用,并且觀察這種效應(yīng)是否有性別依賴性,并研究催產(chǎn)素是否能夠在伏核影響棕色田鼠的焦慮和運(yùn)動(dòng)水平。(1)棕色田鼠自然發(fā)生的不同水平的社會(huì)性與中樞多巴胺、加壓素和催產(chǎn)素的水平及相應(yīng)的多巴胺D1和D2受體、加壓素V1a受體及催產(chǎn)素受體水平的關(guān)系:研究發(fā)現(xiàn)相對(duì)于低社會(huì)性的棕色田鼠,具有高社會(huì)性的田鼠室旁核(PVN)和視上核(SON)具有高水平的催產(chǎn)素陽性神經(jīng)元,在腹側(cè)被蓋區(qū)(VTA)具有高水平的酪氨酸羥化酶(TH)陽性顆粒;而在高社會(huì)性雄性田鼠PVN具有較少的加壓素陽性神經(jīng)元。另一方面,在高社會(huì)性田鼠的伏核發(fā)現(xiàn)有更多的催產(chǎn)素受體的表達(dá),并且發(fā)現(xiàn)高社會(huì)性雄性田鼠在伏核多巴胺D1和D2受體的具有低水平表達(dá)量,而高社會(huì)性雌鼠具有較少的伏核D2受體表達(dá),而在杏仁內(nèi)側(cè)核則較高的D2受體的表達(dá)。(2)棕色田鼠自然發(fā)生的不同水平的親本投資對(duì)社會(huì)性和腦內(nèi)多巴胺、加壓素和催產(chǎn)素水平及多巴胺D1和D2受體、加壓素V1a受體和催產(chǎn)素受體表達(dá)量的影響:研究發(fā)現(xiàn)接受高水平親本投資的雌性和雄性棕色田鼠的社會(huì)性明顯升高,這說明早期親本投資如預(yù)期的一樣可以影響棕色田鼠非繁殖目的的社會(huì)行為。同時(shí),發(fā)現(xiàn)接受高水平親本投資的田鼠室旁核(PVN)和視上核(SON)發(fā)現(xiàn)增多的催產(chǎn)素陽性顆粒,在腹側(cè)被蓋區(qū)(VTA)發(fā)現(xiàn)增多的酪氨酸羥化酶(TH)陽性顆粒,而接受高水平親本投資的雄鼠室旁核發(fā)現(xiàn)減少的加壓素陽性顆粒。此外,研究還發(fā)現(xiàn)早期高水平的親本投資可以顯著增加伏核催產(chǎn)素受體的表達(dá)量,降低雄鼠伏核D1R and D2R mRNA的表達(dá);抑制雌鼠伏核D2R的表達(dá)以及增加雌鼠杏仁內(nèi)側(cè)核D2R的表達(dá)量。(3)在伏核注射催產(chǎn)素及其受體拮抗劑對(duì)社會(huì)接近行為的影響:研究發(fā)現(xiàn)在低社會(huì)性雌性和雄性棕色田鼠伏核內(nèi)微注射催產(chǎn)素可以提高其社會(huì)性,而這種影響具有劑量依賴效應(yīng)。結(jié)果顯示伏核每側(cè)注射1ng催產(chǎn)素可以增加社會(huì)偏好,然而這種影響在較低和較高的劑量中沒有發(fā)現(xiàn)。伏核注射催產(chǎn)素受體拮抗劑,阻斷伏核內(nèi)催產(chǎn)素與其受體的結(jié)合,則可以減少雌性和雄性棕色田鼠的社會(huì)偏好,這種影響也具有劑量依賴效應(yīng),伏核每側(cè)微注射催產(chǎn)素受體拮抗劑10ng和100ng都可以減少社會(huì)接近行為,但是注射1ng的拮抗劑則沒有效果。但是在伏核注射催產(chǎn)素或催產(chǎn)素受體拮抗劑在任何劑量(0.1-10ng/side or 1-100ng/side)都沒有影響棕色田鼠在曠場(chǎng)實(shí)驗(yàn)中的行為。總之,本研究可以得出這樣的結(jié)論:催產(chǎn)素、加壓素和多巴胺系統(tǒng)可以以性別特異性和腦區(qū)特異性的方式調(diào)節(jié)非繁殖目的的社會(huì)行為,自然發(fā)生的不同親本投資不但影響成年后的社會(huì)性,同時(shí)改變了相關(guān)腦區(qū)催產(chǎn)素、加壓素和多巴胺系統(tǒng)參數(shù)的水平,說明早期的不同水平的親本投資可能通過改變這些神經(jīng)化學(xué)物質(zhì)系統(tǒng)影響著成年后的社會(huì)性。此外,研究發(fā)現(xiàn)伏核是催產(chǎn)素影響社會(huì)性的一個(gè)重要腦區(qū)。這些研究結(jié)果在一定程度上闡明了社會(huì)性發(fā)育、形成和調(diào)節(jié)的神經(jīng)內(nèi)分泌機(jī)制。為不同性別低水平社會(huì)性或社交障礙等異常行為的預(yù)防和治療提供新思路。
[Abstract]:The weakening of healthy social interaction and stable social connections is one of the most common symptoms of many mental disorders such as depression, addiction, schizophrenia and autism. Understanding the mechanism and genetic mechanism of normal social connections and development is very important for understanding these mental disorders, and it also provides a possible target for pharmacological intervention and treatment of these diseases. Social connections are common in life activities, which can affect social, psychological, physiological and behavioral functions. The mechanism of the development of social connections is not clear yet, but social connections involve a series of complex processes, including finding companions through feeling, identifying familiar individuals and generating motivation for approaching or contacting. In addition, other acts such as disgust or attack that are not conducive to social connections must be suppressed. Many studies on animals and humans have found that vasopressin, oxytocin, and dopamine can regulate complex social connections. However, most of these reports are focused on the study of vasopressin, oxytocin and dopamine, and the social connections related to reproduction, such as vasopressin, oxytocin and dopamine, which regulate the behavior of parents and their spouses. But there are limited reports on the social links between vasopressin, oxytocin and dopamine and non reproductive purposes. Moreover, changes in early life experience can have a long-term impact on the baby's brain and behavior. Changes in early social environment can cause changes in vasopressin, oxytocin and dopamine system, resulting in systemic changes in physiological function. This change is reflected through reproductive changes related to social behaviors, such as parental behavior and spousal connections. However, the changes in the early social environment are still unclear about the social connections of non reproductive purposes and the long-term effects of the related neuroendocrine mechanisms. In addition, it is difficult to fully explain all the effects of central vasopressin, oxytocin and dopamine on social connections, because these neurotransmitters or conditioner often have R% specificity of species and / or sex, and their effects on social connections are different in different brain regions. There has been a lot of evidence that injection of vasopressin, oxytocin and dopamine at the specific sites of the central nervous system can significantly affect the social connections related to reproduction. The study also showed that the brain regions with vasopressin, oxytocin, and dopamine receptors, such as the nucleus accumbens and the medial amygdala, also regulate the behavior associated with social connections. Then vasopressin, oxytocin and dopamine system in the end what is the relationship between social development and environment of the early animal? Whether hormone and dopamine system and thus affect the social behavior of adult by changing vasopressin, oxytocin? These three systems play a role in the end through which brain regions? In this study, with complex social single preparation of voles as animal models, to explore the social formation and regulation of the neuroendocrine mechanism, this study has three purposes, first, comparison of different naturally occurring social level of mandarin voles, compression element, different expression of oxytocin and dopamine system parameters in the brain; second, naturally occurring voles different levels of social and parental investment whether vasopressin, oxytocin and dopamine system influence. Second, we used Mandarin Microtus fortis as a model to observe whether oxytocin can promote the social behavior of individuals in volt nucleus, and observe whether this effect is gender dependent. We also study whether oxytocin can affect the anxiety and motor level of vole in vole. (1) the relationship between social and different levels of dopamine, vasopressin and oxytocin levels and corresponding dopamine D1 and D2 receptor, vasopressin V1a receptor and oxytocin receptor levels of Microtus mandarinus naturally occurring: the study found that compared to the low social mandarin voles, has high social side room vole nuclear (PVN) and supraoptic nucleus (SON) with high levels of oxytocin immunoreactive neurons in the ventral tegmental area (VTA) with high levels of tyrosine hydroxylase (TH) positive granules; with vasopressin positive neurons less in high social male voles PVN. On the other hand, in the high social vole found expression in nucleus accumbens more oxytocin receptor, and found that high social male voles in the nucleus accumbens dopamine D1 and D2 receptors with low expression and high expression level, social female rats with less D2 receptor in the nucleus accumbens, apricot kernel inside nuclear D2 receptor expression was higher. (2) voles naturally occurring at different levels of dopamine, parental investment on social and brain levels of vasopressin and oxytocin and dopamine D1 and D2 receptors, pressure effect on expression of angiotensin V1a receptor and oxytocin receptor: the study found that the social acceptance of high levels of parental investment of female and male voles significantly this shows that early parental investment increased, as expected can affect the social behavior of voles in non breeding purposes. At the same time, found room voles receive high levels of parental investment (PVN) in the paraventricular nucleus and the supraoptic nucleus (SON) found an increase in oxytocin positive particles in the ventral tegmental area (VTA) found an increase in tyrosine hydroxylase (TH) positive particles, and receive high levels of parental investment in male rat paraventricular nucleus found vasopressin positive granules reduced. In addition, the study also found that early high parental investment significantly increased the expression of oxytocin receptor in nucleus accumbens, reduced the expression of D1R and D2R mRNA in male rats, inhibited the expression of D2R in the nucleus accumbens of female rats and increased the expression of D2R in the medial amygdaloid nucleus of female rats. (3) the effects of oxytocin and its receptor antagonists on social proximity behavior in nucleus accumbens: it is found that microinjection of oxytocin in low social female and male vole voles can improve their social performance.
【學(xué)位授予單位】：陜西師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：Q42

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 邰發(fā)道,王廷正;棕色田鼠洞群內(nèi)社會(huì)組織[J];獸類學(xué)報(bào);2001年01期

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本文編號(hào)：1343511