Summary

从脑边缘和Mesocortical多巴胺奖赏网站继朴素的糖和脂肪摄入大鼠c-fos激活的同时检测

Published: August 24, 2016
doi:

Summary

这项研究的目的是通过使用蜂窝的c-fos的激活来测量大鼠的脂肪和糖新颖摄入后多巴胺途径和终端站点同步变化划定一个可靠免疫组织学技术,以确定奖励相关的分布式脑网络。

Abstract

本研究采用细胞的c-fos的激活来评估脂肪和糖对大鼠脑内多巴胺(DA)的新途径摄入的影响。糖和脂肪摄入量是由他们天生的景点,以及了解到的喜好调节。脑多巴胺,特别是内消旋 – 边缘和从腹侧被盖区(VTA)内消旋 – 皮质突起,已经牵涉在这两个未学习并了解到响应。分布式脑网络,其中的几个位点和发射机/肽系统交互的概念,已提出​​调解适口食物摄入量,但有证据有限经验证明这种行动。因此,糖的摄入引起从个体VTA多巴胺投影区,包括伏隔核(NAC),杏仁核(AMY)DA释放和增加的c-fos的样免疫反应(FLI)和内侧前额叶皮质(mPFC的)以及背侧纹状体。此外,选择性多巴胺受体拮抗剂的集中管理到这些网站Ş差异减少糖类和脂肪引起的空调味的喜好采集和表达。一种方法,借以确定这些网站是否响应糖或脂肪摄入互动作为分布式脑网络将同时评估是否对VTA及其主要mesotelencephalic DA投影区域(前度和伏隔核的infralimbic内侧前额叶皮质,核和壳,基底外侧和中央皮质,内侧AMY)以及背侧纹状体会显示协调,口服后,无条件的摄入玉米油(3.5%),葡萄糖(8%),果糖(8%)和糖精的同时FLI激活(0.2 %)的解决方案。这种方法在鉴别同时使用到相关的大脑部位细胞的c-fos的激活,研究中啮齿类动物的可口食物摄取奖励有关学习的可行性了成功的第一步。

Introduction

脑内多巴胺(DA)已通过牵连到可口的糖的摄入量响应中央提出的享乐1,2,努力有关的3和习惯为基础的行动4,5机制。在这些效应牵连主DA通路起源于腹侧被盖区(VTA),和项目到伏隔核(NAC)芯和壳,基底外侧和中央皮质内侧杏仁核(AMY),以及前度和infralimbic内侧前额叶皮层(内侧前额叶皮质)(查看评论6,7)。该VTA有牵连的蔗糖摄入量8,9,和DA释放后观察糖的摄入量在10-15 NAC,AMY 16,17和内侧前额叶皮质18-20。脂肪的摄入量也刺激多巴胺释放的NAC 21,另有丰富DA投影带的背侧纹状体(尾状核)已与DA介导的喂养22,23也被相关。凯利24-27提出,这些多项目该DA介导系统的离子区形成通过广泛而亲密互连28-34集成和交互的分布式网络的大脑。

除了​​DA D1和D2受体拮抗剂来减少糖35-37和脂肪38-40的摄取的能力,DA信令也已牵涉于介导糖和脂肪以产生调节味道偏好(CFP)的能力41- 46。一个DA D1受体拮抗剂进入NAC,AMY或内侧前额叶皮质47-49显微注射消除CFP的收购胃内引起的葡萄糖。而无论是DA D1或D2受体拮抗剂显微注射到内侧前额叶皮质消除收购果糖CFP 50,收购和果糖CFP表达的差异由NAC和AMY 51,52 DA受体拮抗剂阻断。

在c-fos技术53,54已被用来研究神经活化法制由可口的摄入和神经激活ñ诱导。术语“C-fos的激活”,将整个手稿中使用,并且通过增加的c-Fos蛋白的转录神经元去极化期间可操作限定。蔗糖摄取在中央AMY核增加fos的样免疫反应(FLI),所述VTA以及外壳,但不是核心,在NAC 55-57的。而糖水摄取量假喂养大鼠的AMY和NAC显著上升FLI,但不是VTA 58,胃内蔗糖或葡萄糖输注显著的NAC和AMY 59,60中央和基底外侧核增加FLI。重复加入蔗糖至预定食物访问在mPFC的增加FLI以及在NAC壳和芯61。蔗糖浓度降档模式显示,最大的FLI增加发生在基底AMY和NAC,但不是VTA 62。继空调,糖有关的自然雷瓦灭绝RD行为的基底AMY和NAC 63增加FLI。此外,配对糖可用性达到了口气导致口气随后在基底64 AMY增加FLI水平。高脂肪的摄入量也NAC和内侧前额叶皮质部位增加65-67 FLI。

大多数先前引用的研究中单个位点,不提供关于奖赏相关分布式大脑网络24-27的识别信息检测上的c-fos的激活糖和脂肪的效果。此外,许多研究也没有描绘在NAC(核和壳),AMY(基底和中央皮质内侧)和内侧前额叶皮质的子区域的相对贡献(前度和infralimbic)可能潜在的被检查优势出色的空间,在C-FOS映射68个单细胞的决议。我们的实验室69最近使用的c-fos的激活和同时测量改建的VTA DA通路及其亲jection区(NAC,AMY和内侧前额叶皮质)大鼠脂肪和糖的摄入小说之后。本研究描述的程序和方法步骤,同时分析是否急性暴露六个不同的解决方案(玉米油,葡萄糖,果糖,糖精,水和脂肪乳剂控制)在NAC,AMY的子区域将差异激活FLI,内侧前额叶皮质以及背侧纹状体。这种差异同时检测系统允许的每个站点和决心FLI显著效果的确认,是否与相关网站的变化密切相关,从而为分布式网络的脑支持24-27日在一个特定的站点变化。这些经过测试的程序是否VTA中,前度和infralimbic内侧前额叶皮质的NAC的核心和壳,以及基底和中央皮质,内侧AMY)以及背侧纹状体会显示协调,口服后,无条件的摄入同时FLI激活葡萄糖(8%),果糖(8%),玉米油(3.5%)和糖精(0.2%)的解决方案。

Protocol

这些实验方案已获得批准的机构动物护理和使用委员会证明所有的主体和程序均符合健康指南护理全国学院和实验动物使用。 1.主题购买和/或品种雄性SD大鼠(260 – 300克)。 房子只单独在铁丝网笼子里。保持他们与大鼠饲料和水可随意 12:12小时的光/暗周期。 分配适当的样本大小(例如 ,N≈6 – 8)随机分组。 2.测试仪器和收容程?…

Representative Results

下面描述的所有代表性结果先前已发表​​69,并在此处重新提出支持“概念验证”中指示的技术的有效性。 解决方案摄入量 在基线糖精摄入显著差异观察到在第一四天所有动物(F(3108)= 57.27,P <0.001)与摄入量(第1天:1.3(±0.2)毫升;第2天:3.9(±0.4)毫升;第3天:5.9(±0.6)毫升;第4天:7.1(…

Discussion

这项研究的目的是利用细胞的c-fos的技术来确定源(VTA)和前脑投射目标DA奖励相关的神经元(NAC,AMY,内侧前额叶皮质)的脂肪和糖的新型摄入后同时激活大鼠。本研究是此前69发表的一项研究协议的详细描述。据推测,在VTA,其主要投影区域的前度和infralimbic mPFC的,在NAC的核和壳和基底外侧和中央皮质内侧AMY,以及背侧纹状体将充当分布式脑网络24 -27,并显示协调下同时FLI小?…

Declarações

The authors have nothing to disclose.

Acknowledgements

由于戴安娜卡萨-Culaki,克里斯塔尔桑普森和神学Karagiorgis为他们在这个项目上努力工作。

Materials

Equipment
Sprague-Dawley rats Charles River Laboratories CD-1
Wire Mesh Cages Lab Products, Seaford, DE 30-Cage rack
Rat Chow PMI Nutrition International 5001
Taut Metal Spring Lab Products, Seaford, DE n/a
Rat Weighing Scale Fisher Scientific Company n/a
Nalgene Centrifuge Tubes Lab Products, Seaford, DE 10-0501
Rubber Stopper Lab Products, Seaford, DE n/a
Metal Sippers Lab Products, Seaford, DE n/a
Saccharin Sigma Chemical Co 82385-42-0
Kool-Aid, Cherry Kool-Aid Commerical
Kool-Aid, Grape Kool-Aid Commercial
Fructose Sigma Chemical Co F0127
Glucose Sigma Chemical Co G8270
Corn Oil Mazzola Commerical
Xanthan Gum Sigma Chemical Co 11138-66-2
Sliding Microtome Microm International n/a
Neurolucida Camera MBF Bioscience Software application
Gelatin-coated Slides Fisher Scientific Company 12-550-343
Cover glass Fisher Scientific Company 12-545-M
Golden Nylon Brushes Loew-Cornell  2037
Natural Hair Sable  Loew-Cornell  2022
24 Well Plates Fisher Scientific 3527
6 Well Plates Fisher Scientific 3506
1L Pyrex bottles Fisher Scientific 1395-1L
Tissue insert (tissue strainer) Fisher Scientific 7200214
Eagle pipettes  World Precision Instruments E10 for 1-10ul 
Eagle pipettes  World Precision Instruments E100 for 20-100ul
Eagle pipettes  World Precision Instruments E200 for 50-200ul
Eagle pipettes  World Precision Instruments E1000 for 100-1000ul
Eagle pipettes  World Precision Instruments E5000 for 1000-5000ul 
Universal Tips .1-10ul World Precision Instruments 500192
Universal Tips 5-200ul World Precision Instruments 500194
Universal Tips 500-5000ul World Precision Instruments 500198
Blade Vibroslice 100 World Precision Instruments BLADE
DPX Mounting Medium  Electron Microscopy  13510
15mL centrifuge tubes Biologix Research Co. 10-0501
Slide Boxes Biologix Research Co. 41-6100
Orbital Shaker  Madell Corporation   ZD-9556
weigh boats  Fisher Scientific 02-202-100
5mL disposable pipettes Fisher Scientific 13-711-5AM
Stereo Investigator Software Micro Bright Field Software application
Name Company Catalog number Comments
Reagents
Paraformaldehyde Granular Fisher Scientific 19210
NaCl Fisher Scientific S271-1
Sodium Phophate Monobasic Fisher Scientific S468-500
Sodium Phosphate Diphasic Fisher Scientific BP332-500
Hydrogen Peroxide  Fisher Scientific H324-500
SafeClear II  Fisher Scientific 23-044-192
Methanol  Fisher Scientific A412-1
Normal Goat Serum Vector S-1000
Biotinylated Anti-Rabbit IgG (H+L) Vector BA-1000
ABC Kit Peroxidase Standard Vector PK-4000
Anti-cFos (Ab-5) Rabbit EMD chem/Cal Biochem PC38
Triton X 100 SigmaAldrich X-100
3,3' diaminobenzidine tetra hydrochloride  SigmaAldrich D5905
Sodium Hydroxide SigmaAldrich 5881
Primary TH anti body EMD Millipore AB152
Euthosol Virbac AH

Referências

  1. Koob, G. F. Neural mechanisms of drug reinforcement. Ann. N.Y. Acad. Sci. 654, 171-191 (1992).
  2. Wise, R. A. Role of brain dopamine in food reward and reinforcement. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 361, 1149-1158 (2006).
  3. Salamone, J. D., & Correa, M. The mysterious motivational functions of mesolimbic dopamine. Neuron., 76, 470-485 (2012).
  4. Horvitz, J. C., Choi, W. Y., Morvan, C., Eyny, Y., & Balsam, P.D. A "good parent" function of dopamine: transient modulation of learning and performance during early stages of training. Ann. N.Y. Acad. Sci. 1104, 270-288 (2007).
  5. Wickens, J. R., Horvitz, J. C., Costa, R. M., & Killcross, S. Dopaminergic mechanisms in actions and habits. J. Neurosci. 27, 8181-8183 (2007).
  6. Bjorklund, A., & Dunnett, S. B. Dopamine neuron systems in the brain: an update. Trends Neurosci. 30, 194-202 (2007).
  7. Swanson, L. W. The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res. Bull. 9, 321-353 (1982).
  8. Cacciapaglia, F., Wrightman, R. M., & Careli, R. M. Rapid dopamine signaling differentially modulates distinct microcircuits within the nucleus accumbens during sucrose-directed behavior. J. Neurosci. 31, 13860-13869 (2011).
  9. Martinez-Hernandez, J., Lanuza, E., & Martinez-Garcia, F. Selective dopaminergic lesions of the ventral tegmental area impair preference for sucrose but not for male sex pheromones in female mice. Eur. J. Neurosci. 24, 885-893 (2006).
  10. Bassareo, V., & Di Chiara, G. Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J. Neurosci. 17, 851-861 (1997).
  11. Bassareo, V., & Di Chiara, G. Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments. Neurosci. 89, 637-641, (1999).
  12. Cheng, J, & Feenstra, M.G. Individual differences in dopamine efflux in nucleus accumbens shell and core during instrumental conditioning. Learn. Mem. 13, 168-177 (2006).
  13. Genn, R.F., Ahn, S., & Phillips, A.G. Attenuated dopamine efflux in the rat nucleus accumbens during successive negative contrast. Behav. Neurosci. 118, 869-873 (2004).
  14. Hajnal, A., & Norgren, R. Accumbens dopamine mechanisms in sucrose intake. Brain Res. 904, 76-84 (2001).
  15. Hajnal, A., Smith, G.P., & Norgren, R. Oral sucrose stimulation increases accumbens dopamine in the rat. Am. J. Physiol. 286 R31-R37 (2003).
  16. Bassareo, V., & Di Chiara, G. Modulation of feeding-induced activation of mesolimbic dopamine transmission by appetitive stimuli and its relation to motivational state. Eur. J. Neurosci. 11, 4389-4397 (1999).
  17. Hajnal, A., & Lenard, L. Feeding-related dopamine in the amygdala of freely moving rats. Neuroreport. 8, 2817-2820 (1997).
  18. Bassareo, V., De Luca, M.A., & Di Chiara, G. Differential expression of motivational stimulus properties by dopamine in nucleus accumbens shell versus core and prefrontal cortex. J. Neurosci. 22, 4709-4719 (2002).
  19. Feenstra, M., & Botterblom, M. Rapid sampling of extracellular dopamine in the rat prefrontal cortex during food consumption, handling, and exposure to novelty. Brain Res. 742, 17-24 (1996).
  20. Hernandez, L., & Hoebel, B.G. Feeding can enhance dopamine turnover in the prefrontal cortex. Brain Res. Bull. 25, 975-979 (1990).
  21. Liang, N. C., Hajnal, A., & Norgren, R. Sham feeding corn oil increases accumbens dopamine in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R1236-1239 (2006).
  22. Dunnett, S. B., & Iversen, S. D. Regulatory impairments following selective kainic acid lesions of the neostriatum. Behav. Brain Res. 1, 497-506 (1980).
  23. Salamone, J. D., Zigmond, M. J., & Stricker, E. M. Characterization of the impaired feeding behavior in rats given haloperidol or dopamine-depleting brain lesions. Neurosci. 39, 17-24 (1990).
  24. Kelley, A. E. Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci. Biobehav. Rev. 27, 765-776 (2004).
  25. Kelley, A.E. Memory and addiction: shared neural circuitry and molecular mechanisms. Neuron. 44, 161-179 (2004).
  26. Kelley, A.E., Baldo, B.A., & Pratt, W.E. A proposed hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal and food reward. J. Comp. Neurol. 493, 72-85 (2005).
  27. Kelley, A. E., Baldo, B. A., Pratt, W. E., & Will, M. J. Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol. Behav. 86, 773-795 (2005).
  28. Berendse, H.W., Galis-de-Graaf, Y., & Groenewegen, H.J. Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat. J. Comp. Neurol. 316, 314-347 (1992).
  29. Brog, J.S., Salyapongse, A., Deutch, A.Y., & Zahm, D.S. The patterns of afferent innervation of the core and shell in the "accumbens" part of rat ventral striatum: immunohistochemical detection of retrogradely transported fluoro-gold. J. Comp. Neurol. 338, 255-278 (1993).
  30. McDonald, A.J. Organization of amygdaloid projections to the prefrontal cortex and associated stritum in the rat. Neurosci. 44, 1-14 (1991).
  31. McGeorge, A.J., & Faull, R.L. The organization of the projection from the cerebral cortex to the striatum in the rat. Neurosci. 29, 503-537 (1989).
  32. Sesack, S.R., Deutch, A.Y., Roth, R.H., & Bunney, B.S. Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. J. Comp. Neurol. 290, 213-242 (1989).
  33. Wright, C.I., Beijer, A.V., & Groenewegen, H.J. Basal amygdaloid complex afferents to the rat nucleus accumbens are compartmentally organized. J. Neurosci. 16, 1877-1893 (1996).
  34. Wright, C.I., & Groenewegen, H.J. Patterns of convergence and segregation in the medial nucleus accumbens of the rat: relationships of prefrontal cortical, midline thalamic and basal amygdaloid afferents. J. Comp. Neurol. 361, 383-403 (1995).
  35. Geary, N., & Smith, G.P. Pimozide decreases the positive reinforcing effect of sham fed sucrose in the rat. Pharmacol. Biochem. Behav. 22, 787-790 (1985).
  36. Muscat, R., & Willner, P. Effects of selective dopamine receptor antagonists on sucrose consumption and preference. Psychopharmacol. 99, 98-102 (1989).
  37. Schneider, L.H., Gibbs, J., & Smith, G.P. D-2 selective receptor antagonists suppress sucrose sham feeding in the rat. Brain Res. Bull. 17, 605-611 (1986).
  38. Baker, R.W., Osman, J., & Bodnar, R.J. Differential actions of dopamine receptor antagonism in rats upon food intake elicited by mercaptoacetate or exposure to a palatable high-fat diet. Pharmacol. Biochem. Behav. 69, 201-208 (2001).
  39. Rao, R.E., Wojnicki, F.H., Coupland, J., Ghosh, S., & Corwin, R.L. Baclofen, raclopride and naltrexone differentially reduce solid fat emulsion intake under limited access conditions. Pharmacol. Biochem. Behav. 89, 581-590 (2008).
  40. Weatherford, S.C., Smith, G.P., & Melville, L.D. D-1 and D-2 receptor antagonists decrease corn oil sham feeding in rats. Physiol. Behav. 44, 569-572 (1988).
  41. Azzara, A. V., Bodnar, R. J., Delamater, A. R., & Sclafani, A. D1 but not D2 dopamine receptor antagonism blocks the acquisition of a flavor preference conditioned by intragastric carbohydrate infusions. Pharmacol. Biochem. Behav. 68, 709-720 (2001).
  42. Baker, R. M., Shah, M. J., Sclafani, A., & Bodnar, R. J. Dopamine D1 and D2 antagonists reduce the acquisition and expression of flavor-preferences conditioned by fructose in rats. Pharmacol. Biochem. Behav. 75, 55-65 (2003).
  43. Dela Cruz, J.A., Coke, T., Icaza-Cukali, D., Khalifa, N., & Bodnar, R. J. Roles of NMDA and dopamine D1 and D2 receptors in the acquisition and expression of flavor preferences conditioned by oral glucose in rats. Neurobiol. Learn. Mem. 114, 223-230 (2014).
  44. Dela Cruz, J. A, et al. Roles of dopamine D1 and D2 receptors in the acquisition and expression of fat-conditioned flavor preferences in rats. Neurobiol. Learn. Mem. 97, 332-337 (2012).
  45. Yu, W.Z., Silva, R.M., Sclafani, A., Delamater, A.R., & Bodnar, R.J. Pharmacology of flavor preference conditioning in sham-feeding rats: effects of dopamine receptor antagonists. Pharmacol. Biochem. Behav. 65, 635-647 (2000).
  46. Yu, W. Z., Silva, R. M., Sclafani, A., Delamater, A. R., & Bodnar, R. J. Role of D(1) and D(2) dopamine receptors in the acquisition and expression of flavor-preference conditioning in sham-feeding rats. Pharmacol. Biochem. Behav. 67, 537-544 (2000).
  47. Touzani, K., Bodnar, R. J, & Sclafani, A. Activation of dopamine D1-like receptors in nucleus accumbens is critical for the acquisition, but not the expression, of nutrient-conditioned flavor preferences in rats. Eur. J. Neurosci. 27, 1525-1533 (2008).
  48. Touzani, K., Bodnar, R. J., & Sclafani, A. Dopamine D1-like receptor antagonism in amygdala impairs the acquisition of glucose-conditioned flavor preference in rats. Eur. J. Neurosci. 30, 289-298 (2009).
  49. Touzani, K., Bodnar, R. J., & Sclafani, A. Acquisition of glucose-conditioned flavor preference requires the activation of dopamine D1-like receptors within the medial prefrontal cortex in rats. Neurobiol. Learn. Mem. 94, 214-219 (2010).
  50. Malkusz, D. C., et al. Dopamine signaling in the medial prefrontal cortex and amygdala is required for the acquisition of fructose-conditioned flavor preferences in rats. Behav. Brain Res. 233, 500-507 (2012).
  51. Bernal, S. Y., et al. Role of dopamine D1 and D2 receptors in the nucleus accumbens shell on the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats. Behav. Brain Res. 190, 59-66 (2008).
  52. Bernal, S. Y.,et al. Role of amygdala dopamine D1 and D2 receptors in the acquisition and expression of fructose-conditioned flavor preferences in rats. Behav. Brain Res. 205, 183-190 (2009).
  53. Dragunow, M., & Faull, R. The use of c-fos as a metabolic marker in neuronal pathway tracing. J. Neurosci. Methods. 29, 261-265 (1989).
  54. VanElzakker, M., Fevurly, R. D., Breindel, T., & Spencer, R. L. Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex. Learn. Mem. 15, 899-908 (2008).
  55. Norgren, R., Hajnal, A., & Mungarndee, S. S. Gustatory reward and the nucleus accumbens. Physiol. Behav. 89, 531-535 (2006).
  56. Park, T. H., & Carr, K. D. Neuroanatomical patterns of fos-like immunoreactivity induced by a palatable meal and meal-paired environment in saline- and naltrexone-treated rats. Brain Res. 805, 169-180 (1998).
  57. Zhao, X. L., Yan, J. Q., Chen, K., Yang, X. J., Li, J. R., & Zhang, Y. Glutaminergic neurons expressing c-Fos in the brainstem and amygdala participate in signal transmission and integration of sweet taste. Nan.Fang Yi.Ke.Da.Xue.Xue.Bao. 31,1138-1142 (2011).
  58. Mungarndee, S. S., Lundy, R. F., Jr., & Norgren, R. Expression of Fos during sham sucrose intake in rats with central gustatory lesions. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, R751-R763 (2008).
  59. Otsubo, H., Kondoh, T., Shibata, M., Torii, K., & Ueta, Y. Induction of Fos expression in the rat forebrain after intragastric administration of monosodium L-glutamate, glucose and NaCl. Neurosci. 196, 97-103 (2011).
  60. Yamamoto, T., Sako, N., Sakai, N., & Iwafune, A. Gustatory and visceral inputs to the amygdala of the rat: conditioned taste aversion and induction of c-fos-like immunoreactivity. Neurosci. Lett. 226, 127-130 (1997).
  61. Mitra, A., Lenglos, C., Martin, J., Mbende, N., Gagne, A., & Timofeeva, E. Sucrose modifies c-fos mRNA expression in the brain of rats maintained on feeding schedules. Neurosci. 192, 459-474 (2011).
  62. Pecoraro, N., & Dallman, M. F. c-Fos after incentive shifts: expectancy, incredulity, and recovery. Behav. Neurosci. 119, 366-387 (2005).
  63. Hamlin, A. S., Blatchford, K. E., & McNally, G. P. Renewal of an extinguished instrumental response: Neural correlates and the role of D1 dopamine receptors. Neurosci. 143,.25-38 (2006).
  64. Kerfoot, E. C., Agarwal, I., Lee, H. J., & Holland, P. C. Control of appetitive and aversive taste-reactivity responses by an auditory conditioned stimulus in a devaluation task: A FOS and behavioral analysis. Learn. Mem. 14, 581-589 (2007).
  65. Zhang, M., & Kelley, A.E. Enhanced intake of high-fat food following striatal mu-opioid stimulation: microinjection mapping and fos expression. Neurosci. 99, 267-277 (2000).
  66. Teegarden, S.L., Scott, A.N., & Bale, T.L. Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling. Neurosci. 162, 924-932 (2009).
  67. Del Rio, D., et al. Involvement of the dorsomedial prefrontal cortex in high-fat food conditioning in adolescent mice. Behav. Brain Res. 283, 227-232 (2015).
  68. Knapska, E., Radwanska, K., Werka, T., & Kaczmarek, L. Functional internal complexity of amygdala: focus on gene activity mapping after behavioral training and drugs of abuse. Physiol. Rev. 87, 1113-1173 (2007).
  69. Dela Cruz, J.A.D.,et al. c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats. Brain Res. Bull. 111, 9-19 (2015).
  70. Paxinos, G., & Watson, C. The rat brain in stereotaxic coordinates. Elsevier (2006).
  71. Ranaldi, R., et al. The effects of VTA NMDA receptor antagonism on reward-related learning and associated c-fos expression in forebrain. Behav. Brain Res. 216, 424-432 (2011).
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Dela Cruz, J. A. D., Coke, T., Bodnar, R. J. Simultaneous Detection of c-Fos Activation from Mesolimbic and Mesocortical Dopamine Reward Sites Following Naive Sugar and Fat Ingestion in Rats. J. Vis. Exp. (114), e53897, doi:10.3791/53897 (2016).

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