Research Article
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The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats

Year 2021, Volume: 38 Issue: 3, 331 - 335, 01.05.2021

Hayriye Soytürk Bihter Gökçe Bozat Hamit Coşkun Fatma Pehlivan Karakaş

Abstract

Leptin is released by adipose tissue. Leptin can cross the blood–brain barrier and bind to receptors on neurons in brain areas to exert its biological function when released into circulation. This study aimed to determine the influences of intraamygdalar administration of high and low doses of leptin on anxiety, depression, learning behaviors of rats. In the experimental protocol I, intraamygdalar injection of high and low doses of leptin (0.1 and 1 μg/ kg) and saline were administered 30 min before the behavioral tests. Then, the animals were exposed to open field, elevated plus maze, Porsolt and Morris water maze tests for measuring of behaviors. In experimental protocol 2, the cerebrospinal fluids of all groups of experimental protocol 1 were collected by microdialysis method and then were analyzed by HPLC.The effect of the low dose of leptin was significant on the open field. The effect of the high and low dose of leptin was significant on the elevated plus maze test. The effect of the low dose of leptin was significant on mobility in the center of the Porsolt. A high dose of leptin group had spent less time around the platform than controls in the Morris water maze test. HPLC analysis showed that the amount of serotonin and glutamate in the amygdala region increased after low dose leptin administration. Intraamygdalar injection of low doses of leptin may decrease anxiety and depression-like behavior in rats by increasing serotonin and glutamate levels in the amygdala.

Keywords

Leptin Behaviors amygdala anxiety depression Learning

Supporting Institution

Bolu Abant İzzet Baysal Üniversitesi

Project Number

2012.03.01.504

Thanks

The authors would like to thank Alper Karakaş Laboratory for laboratory equipment support in the Department of Biology, Bolu Abant Izzet Baysal University, Bolu, Turkey. This study was financed by the Bolu Abant İzzet Baysal University Research Foundation (Project No: 2012.03.01.504).

References

  • Banks, A. S., Davis, S. M., Bates, S. H., & Myers, M. G., Jr.,2000. Activation of downstream signals by the long form of the leptin receptor. The Journal of biological chemistry, 275(19), 14563–14572. https://doi.org/10.1074/jbc.275.19.14563
  • Berridge, K. C., & Kringelbach, M. L.,2015. Pleasure systems in the brain. Neuron, 86(3), 646–664. https://doi.org/10.1016/j.neuron.2015.02.018 Canli T, Omura K, Haas BW Fallgatter A, Constable RT, Lesch KP., Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task. PNAS. 2005;102:12224-29.
  • De Kloet, E. R., Joëls, M., & Holsboer, F.,2005. Stress and the brain: from adaptation to disease. Nature reviews. Neuroscience, 6(6), 463–475. https://doi.org/10.1038/nrn1683
  • Esel, E., Ozsoy, S., Tutus, A., Sofuoglu, S., Kartalci, S., Bayram, F., Kokbudak, Z., & Kula, M.,2005. Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression. Progress in neuro-psychopharmacology & biological psychiatry, 29(4), 565–570. https://doi.org/10.1016/j.pnpbp.2005.01.009
  • Farr, S. A., Banks, W. A., & Morley, J. E., 2006. Effects of leptin on memory processing. Peptides, 27(6), 1420–1425. https://doi.org/10.1016/j.peptides.2005.10.006
  • Havel P. J., 2000. Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. The Proceedings of the Nutrition Society, 59(3), 359–371. https://doi.org/10.1017/s0029665100000410
  • Heiman, M. L., Ahima, R. S., Craft, L. S., Schoner, B., Stephens, T. W., & Flier, J. S.,1997. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology, 138(9), 3859–3863. https://doi.org/10.1210/endo.138.9.5366
  • Hastings, R.P.,2002. Parental stress and behaviour problems of children with developmental disability. J Intellect Dev Disabil.;27:149-160. Jow GM, Yang TT, Chen CL., 2006. Leptin and cholesterol levels are low in major depressive disorder, but high in schizophrenia. Journal of Affective Disorders. 90(1):21-27. DOI: 10.1016/j.jad.2005.09.015.
  • Kanoski, S. E., & Davidson, T. L.,2011. Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiology & behavior, 103(1), 59–68. https://doi.org/10.1016/j.physbeh.2010.12.003
  • Krishnan, V., & Nestler, E. J., 2010. Linking molecules to mood: new insight into the biology of depression. The American journal of psychiatry, 167 (11), 1305–1320. https://doi.org/10.1176/appi.ajp.2009.10030434
  • Kraus, T., Haack, M., Schuld, A., Hinze-Selch, D., Koethe, D., & Pollmächer, T., 2002. Body weight, the tumor necrosis factor system, and leptin production during treatment with mirtazapine or venlafaxine. Pharmacopsychiatry, 35(6), 220–225. https://doi.org/10.1055/s-2002-36390
  • Kurhe, Y., Mahesh, R., & Devadoss, T ., 2015. QCM-4, a 5-HT₃ receptor antagonist ameliorates plasma HPA axis hyperactivity, leptin resistance and brain oxidative stress in depression and anxiety-like behavior in obese mice. Biochemical and biophysical research communications, 456(1), 74–79. https://doi.org/10.1016/j.bbrc.2014.11.036
  • Liu, T., Yuan, Z., Sun, J., Wang, J., Zheng, N., Tang, X., & Shum, H. Y., 2011. Learning to detect a salient object. IEEE transactions on pattern analysis and machine intelligence, 33(2), 353–367. https://doi.org/10.1109/TPAMI.2010.70
  • Liu, C., Kelnar, K., Liu, B., Chen, X., Calhoun-Davis, T., Li, H., Patrawala, L., Yan, H., Jeter, C., Honorio, S., Wiggins, J. F., Bader, A. G., Fagin, R., Brown, D., & Tang, D. G., 2011. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nature medicine, 17(2), 211–215. https://doi.org/10.1038/nm.2284
  • Lu, A. H., Salabas, E. L., & Schüth, F.,2007. Magnetic nanoparticles: synthesis, protection, functionalization, and application. Angewandte Chemie (International ed. in English), 46(8), 1222–1244. https://doi.org/10.1002/anie.200602866
  • Liu, J., Guo, M., & Lu, X. Y.,2015. Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors. The international journal of neuropsychopharmacology, 19(2), pyv115. https://doi.org/10.1093/ijnp/pyv115
  • Patterson P. H., 2011. Maternal infection and immune involvement in autism. Trends in molecular medicine, 17(7), 389–394. https://doi.org/10.1016/j.molmed.2011.03.001
  • Pasco, J. A., Williams, L. J., Jacka, F. N., Ng, F., Henry, M. J., Nicholson, G. C., Kotowicz, M. A., & Berk, M.,2008. Tobacco smoking as a risk factor for major depressive disorder: population-based study. The British journal of psychiatry : the journal of mental science, 193(4), 322–326. https://doi.org/10.1192/bjp.bp.107.046706
  • Paulus, K., Schulz, C., & Lehnert, H.,2005. Central nervous effects of leptin and insulin on hippocampal leptin and insulin receptor expression following a learning task in Wistar rats. Neuropsychobiology, 51(2), 100–106. https://doi.org/10.1159/000084167
  • Reseland JE, Mundal HH, Hollung K, et al.,2005. Cigarette smoking may reduce plasma leptin concentration via catecholamines. Prostaglandins, Leukotrienes, and Essential Fatty Acids. Jul;73(1):43-49. DOI: 10.1016/j.plefa.2005.04.006.
  • Rubin, K. H., Burgess, K. B., & Hastings, P. D.,2002. Stability and social-behavioral consequences of toddlers' inhibited temperament and parenting behaviors. Child development, 73(2), 483–495. https://doi.org/10.1111/1467-8624.00419
  • Romanova, I. V., Derkach, K. V., Mikhrina, A. L., Sukhov, I. B., Mikhailova, E. V., & Shpakov, A. O.,2018. The Leptin, Dopamine and Serotonin Receptors in Hypothalamic POMC-Neurons of Normal and Obese Rodents. Neurochemical research, 43(4), 821–837. https://doi.org/10.1007/s11064-018-2485-z
  • Sharma, A. N., Elased, K. M., Garrett, T. L., & Lucot, J. B.,2010. Neurobehavioral deficits in db/db diabetic mice. Physiology & behavior, 101(3), 381–388. https://doi.org/10.1016/j.physbeh.2010.07.002
  • Schilling, T. M., Kölsch, M., Larra, M. F., Zech, C. M., Blumenthal, T. D., Frings, C., & Schächinger, H.,2013. For whom the bell (curve) tolls: cortisol rapidly affects memory retrieval by an inverted U-shaped dose-response relationship. Psychoneuroendocrinology, 38(9), 1565–1572. https://doi.org/10.1016/j.psyneuen.2013.01.001
  • Tecott, L. H., Maricq, A. V., & Julius, D.,1993. Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proceedings of the National Academy of Sciences of the United States of America, 90(4), 1430–1434. https://doi.org/10.1073/pnas.90.4.1430
  • Yu, W. H., Kimura, M., Walczewska, A., Karanth, S., & McCann, S. M.,1997. Role of leptin in hypothalamic-pituitary function. Proceedings of the National Academy of Sciences of the United States of America, 94(3), 1023–1028. https://doi.org/10.1073/pnas.94.3.1023
  • Zarrindast, M. R., & Khakpai, F.,2015. The Modulatory Role of Dopamine in Anxiety-like Behavior. Archives of Iranian medicine, 18(9), 591–603.
  • Zhang, Y., Proenca, R., Maffei, M. et al.,1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 https://doi.org/10.1038/372425a0
  • Zeman, M., Szántóová, K., Stebelová, K., Mravec, B., & Herichová, I., 2009. Effect of rhythmic melatonin administration on clock gene expression in the suprachiasmatic nucleus and the heart of hypertensive TGR (mRen2)27 rats. Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 27(6), S21–S26. https://doi.org/10.1097/01.hjh.0000358833.41181.f6

Year 2021, Volume: 38 Issue: 3, 331 - 335, 01.05.2021

Hayriye Soytürk Bihter Gökçe Bozat Hamit Coşkun Fatma Pehlivan Karakaş

Abstract

Project Number

2012.03.01.504

References

  • Banks, A. S., Davis, S. M., Bates, S. H., & Myers, M. G., Jr.,2000. Activation of downstream signals by the long form of the leptin receptor. The Journal of biological chemistry, 275(19), 14563–14572. https://doi.org/10.1074/jbc.275.19.14563
  • Berridge, K. C., & Kringelbach, M. L.,2015. Pleasure systems in the brain. Neuron, 86(3), 646–664. https://doi.org/10.1016/j.neuron.2015.02.018 Canli T, Omura K, Haas BW Fallgatter A, Constable RT, Lesch KP., Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task. PNAS. 2005;102:12224-29.
  • De Kloet, E. R., Joëls, M., & Holsboer, F.,2005. Stress and the brain: from adaptation to disease. Nature reviews. Neuroscience, 6(6), 463–475. https://doi.org/10.1038/nrn1683
  • Esel, E., Ozsoy, S., Tutus, A., Sofuoglu, S., Kartalci, S., Bayram, F., Kokbudak, Z., & Kula, M.,2005. Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression. Progress in neuro-psychopharmacology & biological psychiatry, 29(4), 565–570. https://doi.org/10.1016/j.pnpbp.2005.01.009
  • Farr, S. A., Banks, W. A., & Morley, J. E., 2006. Effects of leptin on memory processing. Peptides, 27(6), 1420–1425. https://doi.org/10.1016/j.peptides.2005.10.006
  • Havel P. J., 2000. Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. The Proceedings of the Nutrition Society, 59(3), 359–371. https://doi.org/10.1017/s0029665100000410
  • Heiman, M. L., Ahima, R. S., Craft, L. S., Schoner, B., Stephens, T. W., & Flier, J. S.,1997. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology, 138(9), 3859–3863. https://doi.org/10.1210/endo.138.9.5366
  • Hastings, R.P.,2002. Parental stress and behaviour problems of children with developmental disability. J Intellect Dev Disabil.;27:149-160. Jow GM, Yang TT, Chen CL., 2006. Leptin and cholesterol levels are low in major depressive disorder, but high in schizophrenia. Journal of Affective Disorders. 90(1):21-27. DOI: 10.1016/j.jad.2005.09.015.
  • Kanoski, S. E., & Davidson, T. L.,2011. Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiology & behavior, 103(1), 59–68. https://doi.org/10.1016/j.physbeh.2010.12.003
  • Krishnan, V., & Nestler, E. J., 2010. Linking molecules to mood: new insight into the biology of depression. The American journal of psychiatry, 167 (11), 1305–1320. https://doi.org/10.1176/appi.ajp.2009.10030434
  • Kraus, T., Haack, M., Schuld, A., Hinze-Selch, D., Koethe, D., & Pollmächer, T., 2002. Body weight, the tumor necrosis factor system, and leptin production during treatment with mirtazapine or venlafaxine. Pharmacopsychiatry, 35(6), 220–225. https://doi.org/10.1055/s-2002-36390
  • Kurhe, Y., Mahesh, R., & Devadoss, T ., 2015. QCM-4, a 5-HT₃ receptor antagonist ameliorates plasma HPA axis hyperactivity, leptin resistance and brain oxidative stress in depression and anxiety-like behavior in obese mice. Biochemical and biophysical research communications, 456(1), 74–79. https://doi.org/10.1016/j.bbrc.2014.11.036
  • Liu, T., Yuan, Z., Sun, J., Wang, J., Zheng, N., Tang, X., & Shum, H. Y., 2011. Learning to detect a salient object. IEEE transactions on pattern analysis and machine intelligence, 33(2), 353–367. https://doi.org/10.1109/TPAMI.2010.70
  • Liu, C., Kelnar, K., Liu, B., Chen, X., Calhoun-Davis, T., Li, H., Patrawala, L., Yan, H., Jeter, C., Honorio, S., Wiggins, J. F., Bader, A. G., Fagin, R., Brown, D., & Tang, D. G., 2011. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nature medicine, 17(2), 211–215. https://doi.org/10.1038/nm.2284
  • Lu, A. H., Salabas, E. L., & Schüth, F.,2007. Magnetic nanoparticles: synthesis, protection, functionalization, and application. Angewandte Chemie (International ed. in English), 46(8), 1222–1244. https://doi.org/10.1002/anie.200602866
  • Liu, J., Guo, M., & Lu, X. Y.,2015. Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors. The international journal of neuropsychopharmacology, 19(2), pyv115. https://doi.org/10.1093/ijnp/pyv115
  • Patterson P. H., 2011. Maternal infection and immune involvement in autism. Trends in molecular medicine, 17(7), 389–394. https://doi.org/10.1016/j.molmed.2011.03.001
  • Pasco, J. A., Williams, L. J., Jacka, F. N., Ng, F., Henry, M. J., Nicholson, G. C., Kotowicz, M. A., & Berk, M.,2008. Tobacco smoking as a risk factor for major depressive disorder: population-based study. The British journal of psychiatry : the journal of mental science, 193(4), 322–326. https://doi.org/10.1192/bjp.bp.107.046706
  • Paulus, K., Schulz, C., & Lehnert, H.,2005. Central nervous effects of leptin and insulin on hippocampal leptin and insulin receptor expression following a learning task in Wistar rats. Neuropsychobiology, 51(2), 100–106. https://doi.org/10.1159/000084167
  • Reseland JE, Mundal HH, Hollung K, et al.,2005. Cigarette smoking may reduce plasma leptin concentration via catecholamines. Prostaglandins, Leukotrienes, and Essential Fatty Acids. Jul;73(1):43-49. DOI: 10.1016/j.plefa.2005.04.006.
  • Rubin, K. H., Burgess, K. B., & Hastings, P. D.,2002. Stability and social-behavioral consequences of toddlers' inhibited temperament and parenting behaviors. Child development, 73(2), 483–495. https://doi.org/10.1111/1467-8624.00419
  • Romanova, I. V., Derkach, K. V., Mikhrina, A. L., Sukhov, I. B., Mikhailova, E. V., & Shpakov, A. O.,2018. The Leptin, Dopamine and Serotonin Receptors in Hypothalamic POMC-Neurons of Normal and Obese Rodents. Neurochemical research, 43(4), 821–837. https://doi.org/10.1007/s11064-018-2485-z
  • Sharma, A. N., Elased, K. M., Garrett, T. L., & Lucot, J. B.,2010. Neurobehavioral deficits in db/db diabetic mice. Physiology & behavior, 101(3), 381–388. https://doi.org/10.1016/j.physbeh.2010.07.002
  • Schilling, T. M., Kölsch, M., Larra, M. F., Zech, C. M., Blumenthal, T. D., Frings, C., & Schächinger, H.,2013. For whom the bell (curve) tolls: cortisol rapidly affects memory retrieval by an inverted U-shaped dose-response relationship. Psychoneuroendocrinology, 38(9), 1565–1572. https://doi.org/10.1016/j.psyneuen.2013.01.001
  • Tecott, L. H., Maricq, A. V., & Julius, D.,1993. Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proceedings of the National Academy of Sciences of the United States of America, 90(4), 1430–1434. https://doi.org/10.1073/pnas.90.4.1430
  • Yu, W. H., Kimura, M., Walczewska, A., Karanth, S., & McCann, S. M.,1997. Role of leptin in hypothalamic-pituitary function. Proceedings of the National Academy of Sciences of the United States of America, 94(3), 1023–1028. https://doi.org/10.1073/pnas.94.3.1023
  • Zarrindast, M. R., & Khakpai, F.,2015. The Modulatory Role of Dopamine in Anxiety-like Behavior. Archives of Iranian medicine, 18(9), 591–603.
  • Zhang, Y., Proenca, R., Maffei, M. et al.,1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 https://doi.org/10.1038/372425a0
  • Zeman, M., Szántóová, K., Stebelová, K., Mravec, B., & Herichová, I., 2009. Effect of rhythmic melatonin administration on clock gene expression in the suprachiasmatic nucleus and the heart of hypertensive TGR (mRen2)27 rats. Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 27(6), S21–S26. https://doi.org/10.1097/01.hjh.0000358833.41181.f6
There are 29 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Clinical Research
Authors

Hayriye Soytürk 0000-0002-0000-3768

Bihter Gökçe Bozat 0000-0002-6793-6888

Hamit Coşkun 0000-0002-5509-8717

Fatma Pehlivan Karakaş 0000-0001-5245-6294

Project Number 2012.03.01.504
Publication Date May 1, 2021
Submission Date February 6, 2021
Acceptance Date February 27, 2021
Published in Issue Year 2021 Volume: 38 Issue: 3

Cite

APA Soytürk, H., Bozat, B. G., Coşkun, H., Pehlivan Karakaş, F. (2021). The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats. Journal of Experimental and Clinical Medicine, 38(3), 331-335.
AMA Soytürk H, Bozat BG, Coşkun H, Pehlivan Karakaş F. The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats. J. Exp. Clin. Med. May 2021;38(3):331-335.
Chicago Soytürk, Hayriye, Bihter Gökçe Bozat, Hamit Coşkun, and Fatma Pehlivan Karakaş. “The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats”. Journal of Experimental and Clinical Medicine 38, no. 3 (May 2021): 331-35.
EndNote Soytürk H, Bozat BG, Coşkun H, Pehlivan Karakaş F (May 1, 2021) The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats. Journal of Experimental and Clinical Medicine 38 3 331–335.
IEEE H. Soytürk, B. G. Bozat, H. Coşkun, and F. Pehlivan Karakaş, “The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats”, J. Exp. Clin. Med., vol. 38, no. 3, pp. 331–335, 2021.
ISNAD Soytürk, Hayriye et al. “The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats”. Journal of Experimental and Clinical Medicine 38/3 (May 2021), 331-335.
JAMA Soytürk H, Bozat BG, Coşkun H, Pehlivan Karakaş F. The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats. J. Exp. Clin. Med. 2021;38:331–335.
MLA Soytürk, Hayriye et al. “The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats”. Journal of Experimental and Clinical Medicine, vol. 38, no. 3, 2021, pp. 331-5.
Vancouver Soytürk H, Bozat BG, Coşkun H, Pehlivan Karakaş F. The Effect of Intraamygdalar Leptin Administration on Anxiety, Depression and Learning Behaviors in Rats. J. Exp. Clin. Med. 2021;38(3):331-5.
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