Neuropeptide Y Increases Both Ingestion of a Self-Selection Macronutrient Diet and Fos Expression in the Medial Amygdala of Rats

Bruna Mombach Dietrich, Marli Sita Scalcon, Franklin Back, Bárbara B. Philippi Martins, Elisa Cristiana Winkelmann-Duarte, Alberto A. Rasia-Filho

Departments of Pharmacology and Morphological Sciences, Federal University of Santa Catarina, Florianopolis, Brazil;.
Graduation Course in Pathology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil;.

DOI: 10.4236/nm.2013.43020                

Abstract

The rat posterodorsal medial amygdala (MePD) is responsive to the orexigenic neuropeptide Y (NPY) and is a putative candidate to participate in neural circuits that modulate feeding behavior. Here, we studied the effects of intracerebroventricular (icv) microinjection of NPY on the appetitive and food intake behaviors of rats under the paradigm of the self-selection macronutrient isolated diets [high-carbohydrate (high-CHO), high-protein and high-lipid food pellets]. At the same time, Fos expression was also evaluated in the MePD as a marker of local cellular activation. Adult male rats received icv microinjections of NPY (1mg and10mg/5mL, n = 10 and 8, respectively) whereas the control groups either received icv microinjection of artificial cerebrospinal fluid (5mL, n = 8) or underwent sham procedure (n = 8). The data were obtained after a fasting protocol. Feeding behavior was evaluated during a 2 h test period of free access to the selective diets. Rats in all groups preferred the high-CHO diet. Compared to controls, both doses of NPY increased the appetitive behaviors (searching for food and the frequency of attempts to eat any diet) and the percentage of animals eating high-CHO diet. However, only NPY at a dose of 1 μg led to a significant increase in food intake and showed a strong positive correlation with Fos expression in the MePD (p < 0.05 in all cases). These new data reveal a biphasic effect of NPY on the appetite and food intake behaviors and suggest that the MePD participates in the NPY-induced feeding behavior in rats.

Keywords

Central Control of Appetite; Extended Amygdala; Feeding Behavior; Food Intake Behavior; Motivation

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	H. R. Berthoud, “Multiple Neural Systems Controlling Food Intake and Body Weight,” Neuroscience & Biobehavioral Reviews, Vol. 26, No. 4, 2002, pp. 393-428. doi:10.1016/S0149-7634(02)00014-3
[2]	J. W. Hill, J. K. Elmquist and C. F. Elias, “Hypothalamic Pathways Linking Energy Balance and Reproduction,” American Journal of Physiology: Endocrinology and Metabolism, Vol. 294, No. 5, 2008, pp. E827-E832. doi:10.1152/ajpendo.00670.2007
[3]	K. W. Williams and J. K. Elmquist, “From Neuroanatomy to Behavior: Central Integration of Peripheral Signals Regulating Feeding Behavior,” Nature Neuroscience, Vol. 15, No. 10, 2012, pp. 1350-1355. doi:10.1038/nn.3217
[4]	L. M. Zeltser, R. J. Seeley and M. H. Tschop, “Synaptic Plasticity in Neuronal Circuits Regulating Energy Balance,” Nature Neuroscience, Vol. 15, No. 10, 2012, pp. 1336-1342. doi:10.1038/nn.3219
[5]	A. A. Ammar, F. Sederholm, T. R. Saito, A. J. W. Scheurink, A. E. Johnson and P. Soderstern, “NPY-Leptin: Opposing Effects on Appetitive and Consummatory Ingestive Behavior and Sexual Behavior,” American Journal of Physiology, Vol. 278, No. 6, 2000, pp. 1627-1633.
[6]	G. D. Petrovich, “Forebrain Networks and the Control of Feeding by Environmental Learned Cues,” Physiology & Behavior, 2013, in Press. doi:10.1016/j.physbeh.2013.03.024
[7]	B. G. Stanley, V. L. Willett, H. W. Donias, L. H. Ha and L. C. Spears, “The Lateral Hypothalamus: A Primary Site Mediating Excitatory Amino Acid-Elicited Eating,” Brain Research, Vol. 630, No. 1-2, 1993, pp. 41-49. doi:10.1016/0006-8993(93)90640-9
[8]	M. A. Duva, E. M. Tomkins, L. M. Moranda, R. Kaplan, A. Sukhaseum, A. Jimenez and B. G. Stanley, “Reverse Microdialysis of N-Methyl-D-Aspartic Acid into the Lateral Hypothalamus of Rats: Effects on Feeding and Other Behaviors,” Brain Research, Vol. 921, No. 1-2, 2001, pp. 122-132. doi:10.1016/S0006-8993(01)03108-0
[9]	S. W. Lee and B. G. Stanley, “NMDA Receptors Mediate Feeding Elicited by Neuropeptide Y in the Lateral and Perifornical Hypothalamus,” Brain Research, Vol. 1063, No. 1, 2005, pp. 1-8. doi:10.1016/j.brainres.2005.09.045
[10]	G. D. Petrovich, “Learning and the Motivation to Eat: Forebrain Circuitry,” Physiology & Behavior, Vol. 104, No. 4, 2011, pp. 582-589. doi:10.1016/j.physbeh.2011.04.059
[11]	J. Maniam and M. J. Morris, “The Link between Stress and Feeding Behaviour,” Neuropharmacology, Vol. 63, No. 1, 2012, pp. 97-110. doi:10.1016/j.neuropharm.2012.04.017
[12]	Z. Han, J. Q. Yan, G. G. Luo, Y. Liu and Y. Wang, “Leptin Receptor Expression in the Basolateral Nucleus of Conditioned Taste Aversion,” World Journal of Gastroenterology, Vol. 9, No. 5, 2003, pp. 1034-1037.
[13]	T. Huang, J. Yan and Y. Kang, “Role of the Central Amygdaloid Nucleus in Shaping the Discharge of Gustatory Neurons in the Rat Parabrachial Nucleus,” Brain Research Bulletin, Vol. 61, No. 4, 2003, pp. 443-452. doi:10.1016/S0361-9230(03)00170-9
[14]	C. B. Rosa, J. F. Goularte, N. A. Trindade, A. P. De Oliveira and A. A. Rasia-Filho, “Glutamate Microinjected in the Posterodorsal Medial Amygdala Induces Subtle Increase in the Consumption of a Three-Choice Macronutrient Self-Selection Diet in Male Rats,” Anat Rec, Vol. 294, 2011, pp. 1226-1232. doi:10.1002/ar.21419
[15]	B. M. King, K. N. Rossiter, S. G. Stines, G. M. Zaharan, J. T. Cook, M. D. Humphries and D. A. York, “Amygdaloid-Lesion Hyperphagia: Impaired Response to Caloric Challenges and Altered Macronutrient Selection,” American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 275, No. 2, 1998, pp. R485R493.
[16]	B. M. King, J. T. Cook, K. N. Rossiter and B. L. Rollins, “Obesity-Inducing Amygdala Lesions: Examination of Anterograde Degeneration and Retrograde Transport,” American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 284, No. 4, 2003, pp. R965-R982.
[17]	B. L. Rollins and B. M. King, “Amygdala-Lesion Obesity: What Is the Role of the Various Amygdaloid Nuclei?” merican Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 279, No. 4, 2000, pp. R1348-R1356.
[18]	J. S. de Olmos, C. A. Beltramino and G. Alheid, “Amygdala and Extended Amygdala of the Rat: A Cytoarchitectonical, Fibroarchitectonical, and Chemoarchitectonical Survey,” In: G. Paxinos, Ed., The Rat Nervous System, Elsevier Academic Press, Amsterdam, 2004, pp. 509-603.
[19]	A. Dall’Oglio, G. Gehlen, M. Achaval and A. A. RasiaFilho, “Dendritic Branching Features of Posterodorsal Medial Amygdala Neurons of Adult Male and Female Rats: Further Data Based on the Golgi Method,” Neuroscience Letters, Vol. 430, No. 2, 2008, pp. 151-156. doi:10.1016/j.neulet.2007.10.051
[20]	A. Dall’Oglio, G. Gehlen, M. Achaval and A. A. RasiaFilho, “Dendritic Branching Features of Golgi-Impregnated Neurons from the ‘Ventral’ Medial Amygdala Subnuclei of Adult Male and Female Rats,” Neuroscience Letters, Vol. 439, No. 3, 2008, pp. 287-292. doi:10.1016/j.neulet.2008.05.025
[21]	A. A. Rasia-Filho, F. Dalpian, I. C. Menezes, J. Brusco, J. E. Moreira and R. S. Cohen, “Dendritic Spines of the Medial Amygdala: Plasticity, Density, Shape, and Subcellular Modulation by Sex Steroids,” Histology and Histopathology, Vol. 27, No. 8, 2012, pp. 985-1011.
[22]	A. A. Rasia-Filho, D. Haas, A. P. De Oliveira, J. de Castilhos, R. Frey, D. Stein, V. M. Lazzari, F. Back, G. N. Pires, E. Pavesi, E. C. Winkelmann-Duarte and M. Giovenardi, “Morphological and Functional Features of the Sex Steroid-Responsive Posterodorsal Medial Amygdala of Adult Rats,” Mini-Reviews in Medicinal Chemistry, Vol. 12, No. 11, 2012, pp. 1090-1106. doi:10.2174/138955712802762211
[23]	A. M. Poulin, C. Lenglos, A. Mitra and E. Timofeeva, “Hypothalamic Expression of Urocortin 3 and the Type 2 Corticotropin-Releasing Factor Receptor Is Regulated According to Feeding State in Lean but Not Obese Zucker Rats,” Neuropharmacology, Vol. 63, No. 1, 2012, pp. 147-153. doi:10.1016/j.neuropharm.2011.12.023
[24]	E. Quagliotto, H. Neckel, D. F. Riveiro, K. R. Casali, C. Mostarda, M. C. Irigoyen, P. Dall’Ago and A. A. RasiaFilho, “Histamine in the Posterodorsal Medial Amygdala Modulates Cardiovascular Reflex Responses in Awake Rats,” Neuroscience, Vol. 157, No. 4, 2008, pp. 709-719. doi:10.1016/j.neuroscience.2008.09.053
[25]	H. Neckel, E. Quagliotto, K. R. Casali, N. Montano, P. Dal Lago and A. A. Rasia-Filho, “Glutamate and GABA in the Medial Amygdala Induce Selective Central Sympathetic/Parasympathetic Cardiovascular Responses,” Canadian Journal of Physiology and Pharmacology, Vol. 90, No. 5, 2012, pp. 525-536. doi:10.1139/y2012-024
[26]	S. W. Newman, “The Medial Extended Amygdala in Male Reproductive Behavior. A Node in the Mammalian Social Behavior Network,” Annals of the New York Academy of Sciences, Vol. 877, 1999, pp. 242-257. doi:10.1111/j.1749-6632.1999.tb09271.x
[27]	H. W. Dong, G. Petrovich and L. W. Swanson, “Topography of Projections from Amygdala to Bed Nuclei of the Stria Terminalis,” Brain Research Reviews, Vol. 38, No. 1-2, 2001, pp. 192-246. doi:10.1016/S0165-0173(01)00079-0
[28]	G. D. Petrovich, N. S. Canteras and L. W. Swanson, “Combinatorial Amygdalar Inputs to Hippocampal Domains and Hypothalamic Behavior Systems,” Brain Research Reviews, Vol. 38, No. 1-2, 2001, pp. 247-289. doi:10.1016/S0165-0173(01)00080-7
[29]	B.-H. Li, B. Xu, N. E. Rowland and S. P. Kalra, “c-fos Expression in the Rat Brain Following Central Administration of Neuropeptide Y and Effects of Food Consumption,” Brain Research, Vol. 665, 1994, pp. 272-284. doi:10.1016/0006-8993(94)91348-X
[30]	B. Xu, B.-H. Li, N. E. Rowland and S. P. Kalra, “Neuropeptide Y Injection into the Fourth Cerebroventricle Stimulates c-Fos Expression in the Paraventricular Nucleus and Other Nuclei in the Forebrain: Effect of Food Consumption,” Brain Research, Vol. 698, No. 1-2, 1995, pp. 227-231. doi:10.1016/0006-8993(95)00905-6
[31]	M. Decressac and R. A. Barker, “Neuropeptide Y and Its Role in CNS Disease and Repair,” Experimental Neurology, Vol. 238, No. 2, 2012, pp. 265-272. doi:10.1016/j.expneurol.2012.09.004
[32]	J. F. Flood and J. E. Morley, “Increased Food Intake by Neuropeptide Y Is Due to an Increased Motivation to Eat,” Peptides, Vol. 12, No. 6, 1991, pp. 1329-1332. doi:10.1016/0196-9781(91)90215-B
[33]	M. M. Durkin, M. W. Walker, K. E. Smith, E. L. Gustafson, C. Gerald and T. A. Branchek, “Expression of a Novel Neuropeptide Y Receptor Subtype Involved in Food Intake: An in Situ Hybridization Study of Y5 mRNA Distribution in Rat Brain,” Experimental Neurology, Vol. 165, No. 1, 2000, pp. 90-100. doi:10.1006/exnr.2000.7446
[34]	S. D. Primeaux, D. A. York and G. A. Bray, “Neuropeptide Y Administration into the Amygdala Alters High Fat Food Intake,” Peptides, Vol. 27, No. 7, 2006, pp. 1644-1651. doi:10.1016/j.peptides.2005.12.009
[35]	W. Nicholas, R. Stewart and N. E. Badia-Elder, “Neuropeptide Y Administration into the Amygdala Suppresses Ethanol Drinking in Alcohol-Preferring Rats Following Multiple Deprivations,” Pharmacology Biochemistry and Behavior, Vol. 90, No. 3, 2008, pp. 470-474. doi:10.1016/j.pbb.2008.04.005
[36]	E. L. Gustafson, J. P. Card and R. Y. Moore, “Neuropeptide Y Localization in the Rat Amygdaloid Complex,” The Journal of Comparative Neurology, Vol. 251, No. 3, 1986, pp. 349-362. doi:10.1002/cne.902510306
[37]	B. M. Chronwall, D. A. Di Maggio, V. J. Massari, V. M. Pickel, D. A. Ruggiero and T. L. O’Donohue, “The Anatomy of Neuropeptide-Y-Containing Neurons in Rat Brain,” Neuroscience, Vol. 15, No. 4, 1985, pp. 1159-1181. doi:10.1016/0306-4522(85)90260-X
[38]	M. L. Wolak, M. R. De Joseph, A. D. Cator, A. S. Mokashi, M. S. Brownfield and J. H. Urban, “Comparative Distribution of Neuropeptide Y Y1 and Y5 Receptors in the Rat Brain by Using Immunohistochemistry,” The Journal of Comparative Neurology, Vol. 464, No. 3, 2003, pp. 285-311. doi:10.1002/cne.10823
[39]	E. L. Gustafson, K. E. Smith, M. M. Durkin, M. W. Walker, C. Gerald, R. Weinshank and T. A. Branchek, “Distribution of the Neuropeptide Y Y2 Receptor mRNA in Rat Central Nervous System,” Molecular Brain Research, Vol. 46, No. 1-2, 1997, pp. 223-235. doi:10.1016/S0169-328X(97)00017-X
[40]	H. Higuchi, “Molecular Analysis of Central Feeding Regulation by Neuropeptide Y (NPY) Neurons with NPY Receptor Small Interfering RNAs (siRNAs),” Neurochemistry International, Vol. 61, No. 6, 2012, pp. 936-941. doi:10.1016/j.neuint.2012.02.029
[41]	G. Paxinos and C. Watson, “The Rat Brain in Stereotaxic Coordinates,” Academic Press, San Diego, 2005.
[42]	N. Hájos, T. J. Ellender, R. Zemankovics, E. O. Mann, R. Exley, S. J. Cragg, T. F. Freund and O. Paulsen, “Maintaining Network Activity in Submerged Hippocampal Slices: Importance of Oxygen Supply,” European Journal of Neuroscience, Vol. 29, No. 2, 2009, pp. 319-327. doi:10.1111/j.1460-9568.2008.06577.x
[43]	B. G. Stanley, D. R. Daniel, A. S. Chin and S. F. Leibowitz, “Paraventricular Nucleus Injection of Peptide YY and Neuropeptide Y Preferentially Enhance Carbohydrate Ingestion,” Peptides, Vol. 6, No. 6, 1985, pp. 1205-1211. doi:10.1016/0196-9781(85)90452-8
[44]	A. F. Cezario, E. R. Ribeiro-Barbosa, M. V. Baldo and N. S. Canteras, “Hypothalamic Sites Responding to Predator Threats—The Role of the Dorsal Premammillary Nucleus in Unconditioned and Conditioned Antipredatory Defensive Behavior,” European Journal of Neuroscience, Vol. 28, No. 5, 2008, pp. 1003-1015.
[45]	S. Kollack-Walker and S. W. Newman, “Mating and Agonistic Behavior Produce Different Patterns of Fos Immunolabeling in the Male Syrian Hamster Brain,” Neuroscience, Vol. 66, No. 3, 1995, pp. 721-736. doi:10.1016/0306-4522(94)00563-K
[46]	L. A. Verhagen, M. C. Luijendijk, J. W. de Groot, L. P. van Dommelen, A. G. Klimstra, R. A. Adan and T. A. Roeling, “Anticipation of Meals during Restricted Feeding Increases Activity in the Hypothalamus in Rats,” European Journal of Neuroscience, Vol. 34, No. 9, 2011, pp. 1485-1491. doi:10.1111/j.1460-9568.2011.07880.x
[47]	S. Bi, Y. J. Kim and F. Zheng, “Dorsomedial Hypothalamic NPY and Energy Balance Control,” Neuropeptides, Vol. 46, No. 6, 2012, pp. 309-314. doi:10.1016/j.npep.2012.09.002
[48]	J. E. Morley, A. S. Levine, B. A. Gosnell, J. Kneip and M. Grace, “Effect of Neuropeptide Y on Ingestive Behaviors in the Rat,” The American Journal of Physiology, Vol. 252, No. 3, 1987, pp. R599-R609.
[49]	C. C. Welch, M. K. Grace, C. J. Billington and A. S. Levine, “Preference and Diet Type Affect Macronutrient Selection after Morphine, NPY, Norepinephrine, and Deprivation,” The American Journal of Physiology, Vol. 266, No. 2, 1994, pp. R426-R433.
[50]	E. Quagliotto, K. R. Casali, P. Dal Lago and A. A. Rasia-Filho, “Neurotransmitter and Neuropeptidergic Modulation of Cardiovascular Responses Evoked by the Posterodorsal Medial Amygdala of Adult Male Rats,” In: D. Yilmazer-Hanke, Ed., Insights into the Amygdala, Nova Science Publishers, Hauppauge, 2012, pp. 139-165.
[51]	A. A. Rasia-Filho, “Is There Anything ‘Autonomous’ in the Nervous System?” Advances in Physiology Education, Vol. 30, No. 1, 2006, pp. 9-12. doi:10.1152/advan.00022.2005
[52]	G. L. Pereno, V. Balaszczuk and C. A. Beltramino, “Detection of Conspecific Pheromones Elicits Fos Expression in GABA and Calcium-Binding Cells of the Rat Vomeronasal System-Medial Extended Amygdala,” Journal of Physiology and Biochemistry, Vol. 67, No. 1, 2011. pp. 71-85. doi:10.1007/s13105-010-0051-5
[53]	C. B. Blake and M. Meredith, “Change in Number and Activation of Androgen Receptor-Immunoreactive Cells in the Medial Amygdala in Response to Chemosensory Input,” Neuroscience, Vol. 190, 2011, pp. 228-238. doi:10.1016/j.neuroscience.2011.05.056
[54]	S. Marcuzzo, A. Dall’Oglio, M. F. Ribeiro, M. Achaval and A. A. Rasia-Filho, “Dendritic Spines in the Posterodorsal Medial Amygdala after Restraint Stress and Ageing in Rats,” Neuroscience Letters, Vol. 424, No. 1, 2007, pp. 16-21. doi:10.1016/j.neulet.2007.07.019
[55]	S. D. Primeaux, S. P. Wilson, M. C. Cusick, D. A. York and M. A. Wilson, “Effects of Altered Amygdalar Neuropeptide Y Expression on Anxiety-Related Behaviors,” Neuropsychopharmacology, Vol. 30, 2005, pp. 1589-1597. doi:10.1038/sj.npp.1300705
[56]	M. Heilig, S. McLoed, M. Brot, S. C. Heinrichs, F. Menzaghi, G. F. Koob and K. T. Britton, “AnxiolyticLike Actions of Neuropeptide Y: Mediation by Y1 Receptors in Amygdala, and Dissociation from Food Intake Effects,” Neuropsychopharmacology, Vol. 8, 1993, pp. 357-363. doi:10.1038/npp.1993.35
[57]	E. Knapska, K. Radwanska, T. Werka and L. Kaczmarek, “Functional Internal Complexity of Amygdala: Focus on Gene Activity Mapping after Behavioral Training and Drugs of Abuse,” Physiological Review, Vol. 87, No. 4, 2007, pp. 1113-1173. doi:10.1152/physrev.00037.2006
[58]	D. L. Drazen, M. D. Wortman, R. J. Seeley and S. C. Woods, “Neuropeptide Y Prepares Rats for Scheduled Feeding,” American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, Vol. 288, No. 6, 2005, pp. 1606-1611.
[59]	A. P. Chambers and S. C. Woods, “The Role of Neuropeptide Y in Energy Homeostasis,” Handbook of Experimental Pharmacology, Vol. 209, 2012, pp. 23-45. doi:10.1007/978-3-642-24716-3_2
[60]	B. D. Sachs, “The Appetitive-Consummatory Distinction: Is This 100-Year-Old Baby Worth Saving? Reply to Ball and Balthazart,” Hormones and Behavior, Vol. 53, No. 2, 2008, pp. 315-318. doi:10.1016/j.yhbeh.2007.11.015