运动诱导大鼠条件性味觉厌恶的脑机制研究
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摘要
味觉刺激与内脏不适感觉相联合,动物可对该味觉刺激产生拒绝和回避行为,称为条件性味觉厌恶(CTA)。近来研究发现,味觉刺激与身体运动相联合后也可诱导动物形成CTA,但参与运动诱导CTA的脑结构尚不清楚,因此,本研究以SD大鼠为对象,分为对照组、糖精刺激组、CTA组、CTA+糖精刺激组,CTA组和CTA+糖精刺激组大鼠,在摄取糖精溶液后负重游泳20 min,直至糖精溶液嗜好比低于30%,对照组和CTA组直接取脑制片,糖精刺激组和CTA+糖精刺激组经口腔插管给以糖精溶液5 ml后取脑制片,用免疫组织化学法检测脑内Fos蛋白表达,并探讨了获得CTA后,毁除最后区(AP)对脑内Fos蛋白表达变化的影响。结果显示:
1.甜味刺激和建立CTA均可诱导臂旁外侧核外侧部(LPBE)、内侧臂旁核外部(MPBE)、丘脑中央内侧核(CM)、丘脑室旁核(PV)、下丘脑外侧区(LH)、基底外侧杏仁核(BLA)、伏核壳部(AcbSh)、外侧隔核腹侧部(LSV)等核团内Fos蛋白表达增多。甜味刺激和建立CTA间不存在交互作用,提示这些脑区与味质辨别、味觉报酬评价以及CTA建立后的行为表达等有关,并且其影响是相对独立的。
2.臂旁外侧核中央部(LPBC)内Fos表达水平,在给以甜味刺激时升高,丘脑前背侧核(AD)、中央杏仁核(CeA)、下丘脑背内侧核背侧部(DMD)内Fos蛋白表达水平,在建立CTA后升高。甜味刺激与建立CTA间存在交互作用。即甜味刺激可诱导正常大鼠上述核团内Fos表达增多,但建立CTA后,甜味刺激对Fos表达的上调作用消失。提示LPBC、CeA、AD和DMD在CTA建立中,与相关感觉信息及行为表达信息的整合有关。
3.甜味刺激诱导内侧杏仁核(Me)内Fos蛋白表达增多,而与CTA建立与否无关;建立CTA诱导孤束核中间部(SolIM)、未定带(ZI)内Fos蛋白表达增多,与甜味刺激无交互作用。说明Me内Fos表达的变化主要与甜味刺激有关,而SolIM和ZI内Fos表达的变化主要与CTA建立有关。
4.毁除AP使已获得的CTA消退加快,给以条件性味觉刺激时,厌恶反应减弱。毁除AP的大鼠LPBC内Fos表达水平显著高于假手术组,而MPBE、LPBE、BLA、AcbSh、伏核中央部(AcbC)、被盖背侧核中央部(DTgC)等核团内的Fos蛋白表达水平显著低于假手术组。提示参与CTA建立和消退过程的脑结构既有关联也有不同。
When taste stimulus is combined with gastrointestinal malaise, animals will refuse to ingest it and escape. This behavior is described as conditioned taste aversion (CTA). It is studied recently that the CTA can also be induced by the association of the gustatory stimulus and the physical exercise, but the brain structures taking part in the CTA are not clear yet. So SD rats used by my experiments were divide into four groups, and they were the control group、the saccharin stimulus group、the CTA group and the CTA with saccharin stimulus group. The rats of the CTA group and the CTA with saccharin stimulus group were given the saccharin solution before a 20 min swimming treatment until the predilection ratio of the saccharin solution was lower than 30%. While the brains of the control group and the CTA group were directly dislodged to be made into sections. The other groups were given the same procedures after intraoral stimuli with 5 ml of the saccharin solution through intraoral cannulas. Fos expression was examined by the immunohistochemistry and explored the change of Fos expression in brains of rats that had been lesioned the area postrema (AP)after having acquired CTA. The results suggested:
1. Fos expression induce by both the seet taste stimulus and the establishment of the CTA increased in the external part of the lateral parabrachial nucleus (LPBE), external part of the medial parabrachial nucleus (MPBE), central medial thalamic nucleus (CM), paraventricular thalamic nucleus(PV), lateral hypothalamic area (LH), basolateral amygdaloid nucleus(BLA), shell area of nucleus accumbens (AcbSh) and ventral part of the lateral septal nucleus (LSV). The sweet taste stimulus and the establishment of CTA were not interactional. This denoted that these brain areas were associated with the discrimination of the gustatory quality, reward value of the taste and the behavioral expression after having acquired CTA. They effected on these brain areas independently.
2. Fos expression enhanced in the central part of the lateral parabrachial nucleus (LPBC) when rats were stimulated by the sweet taste, and Fos expression increased in the anterodorsal thalamic nucleus (AD), central amygdaloid nucleus (CeA) and dorsal part of dorsomedial hypothalamic nucleus (DMD) when rats established the CTA. The sweet taste stimulus interacted with the establishment of the CTA. It is said that Fos expression induced by the sweet taste stimulus increased in these areas above, but did not rise any more after the CTA had been set up. The results suggested that the LPBC, CeA, AD and DMD were involved in integrating the sense information and the information of the behavioral expression.
3. More Fos expression induced by the sweet taste stimulus in the medial amygdaloid nucleus (Me) was not involved in establishing the CTA or not. The increase in Fos expression in the intermediate nucleus of the solitary traits (SolIM) and the zona incerta (ZI) generated after rats had set up the CTA. There was not interaction between the establishment of the CTA and the sweet taste stimulus. This indicated that the sweet taste stimulus was critical for the change of Fos expression in the Me, and the establishment of the CTA was a primary factor for Fos expression in SolIM and ZI.
4. The destruction of the AP could accelerate the extinction of the acquired CTA and decreased aversive reactions when rats were given the conditioned taste stimulus. Fos expression of rats with lesions of the AP was higher significantly than the Sham- lesioned group in the LPBC, but was lower significantly than the Sham- lesioned group in the MPBE, LPBE, BLA, AcbSh, core area of accumbens nucleus (AcbC) and central part of dorsal tegmental nucleus (DTgC). The results suggested that brain areas taking part in the establishment of the CTA were associated with brain areas participating in the extinction of the CTA, but there were differences between them.
1.甜味刺激和建立CTA均可诱导臂旁外侧核外侧部(LPBE)、内侧臂旁核外部(MPBE)、丘脑中央内侧核(CM)、丘脑室旁核(PV)、下丘脑外侧区(LH)、基底外侧杏仁核(BLA)、伏核壳部(AcbSh)、外侧隔核腹侧部(LSV)等核团内Fos蛋白表达增多。甜味刺激和建立CTA间不存在交互作用,提示这些脑区与味质辨别、味觉报酬评价以及CTA建立后的行为表达等有关,并且其影响是相对独立的。
2.臂旁外侧核中央部(LPBC)内Fos表达水平,在给以甜味刺激时升高,丘脑前背侧核(AD)、中央杏仁核(CeA)、下丘脑背内侧核背侧部(DMD)内Fos蛋白表达水平,在建立CTA后升高。甜味刺激与建立CTA间存在交互作用。即甜味刺激可诱导正常大鼠上述核团内Fos表达增多,但建立CTA后,甜味刺激对Fos表达的上调作用消失。提示LPBC、CeA、AD和DMD在CTA建立中,与相关感觉信息及行为表达信息的整合有关。
3.甜味刺激诱导内侧杏仁核(Me)内Fos蛋白表达增多,而与CTA建立与否无关;建立CTA诱导孤束核中间部(SolIM)、未定带(ZI)内Fos蛋白表达增多,与甜味刺激无交互作用。说明Me内Fos表达的变化主要与甜味刺激有关,而SolIM和ZI内Fos表达的变化主要与CTA建立有关。
4.毁除AP使已获得的CTA消退加快,给以条件性味觉刺激时,厌恶反应减弱。毁除AP的大鼠LPBC内Fos表达水平显著高于假手术组,而MPBE、LPBE、BLA、AcbSh、伏核中央部(AcbC)、被盖背侧核中央部(DTgC)等核团内的Fos蛋白表达水平显著低于假手术组。提示参与CTA建立和消退过程的脑结构既有关联也有不同。
When taste stimulus is combined with gastrointestinal malaise, animals will refuse to ingest it and escape. This behavior is described as conditioned taste aversion (CTA). It is studied recently that the CTA can also be induced by the association of the gustatory stimulus and the physical exercise, but the brain structures taking part in the CTA are not clear yet. So SD rats used by my experiments were divide into four groups, and they were the control group、the saccharin stimulus group、the CTA group and the CTA with saccharin stimulus group. The rats of the CTA group and the CTA with saccharin stimulus group were given the saccharin solution before a 20 min swimming treatment until the predilection ratio of the saccharin solution was lower than 30%. While the brains of the control group and the CTA group were directly dislodged to be made into sections. The other groups were given the same procedures after intraoral stimuli with 5 ml of the saccharin solution through intraoral cannulas. Fos expression was examined by the immunohistochemistry and explored the change of Fos expression in brains of rats that had been lesioned the area postrema (AP)after having acquired CTA. The results suggested:
1. Fos expression induce by both the seet taste stimulus and the establishment of the CTA increased in the external part of the lateral parabrachial nucleus (LPBE), external part of the medial parabrachial nucleus (MPBE), central medial thalamic nucleus (CM), paraventricular thalamic nucleus(PV), lateral hypothalamic area (LH), basolateral amygdaloid nucleus(BLA), shell area of nucleus accumbens (AcbSh) and ventral part of the lateral septal nucleus (LSV). The sweet taste stimulus and the establishment of CTA were not interactional. This denoted that these brain areas were associated with the discrimination of the gustatory quality, reward value of the taste and the behavioral expression after having acquired CTA. They effected on these brain areas independently.
2. Fos expression enhanced in the central part of the lateral parabrachial nucleus (LPBC) when rats were stimulated by the sweet taste, and Fos expression increased in the anterodorsal thalamic nucleus (AD), central amygdaloid nucleus (CeA) and dorsal part of dorsomedial hypothalamic nucleus (DMD) when rats established the CTA. The sweet taste stimulus interacted with the establishment of the CTA. It is said that Fos expression induced by the sweet taste stimulus increased in these areas above, but did not rise any more after the CTA had been set up. The results suggested that the LPBC, CeA, AD and DMD were involved in integrating the sense information and the information of the behavioral expression.
3. More Fos expression induced by the sweet taste stimulus in the medial amygdaloid nucleus (Me) was not involved in establishing the CTA or not. The increase in Fos expression in the intermediate nucleus of the solitary traits (SolIM) and the zona incerta (ZI) generated after rats had set up the CTA. There was not interaction between the establishment of the CTA and the sweet taste stimulus. This indicated that the sweet taste stimulus was critical for the change of Fos expression in the Me, and the establishment of the CTA was a primary factor for Fos expression in SolIM and ZI.
4. The destruction of the AP could accelerate the extinction of the acquired CTA and decreased aversive reactions when rats were given the conditioned taste stimulus. Fos expression of rats with lesions of the AP was higher significantly than the Sham- lesioned group in the LPBC, but was lower significantly than the Sham- lesioned group in the MPBE, LPBE, BLA, AcbSh, core area of accumbens nucleus (AcbC) and central part of dorsal tegmental nucleus (DTgC). The results suggested that brain areas taking part in the establishment of the CTA were associated with brain areas participating in the extinction of the CTA, but there were differences between them.
引文
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