The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Preventive Effect of Serotonergic Drugs on LPS-Induced Acute Anorexia in Rats

  • Park, So-Young (Departments of Physiology, College of Medicine, Yeungnam University) ;
  • Kim, Keon-Ho (Departments of Orthopedic Surgery, College of Medicine, Yeungnam University) ;
  • Ahn, Dong-Kuk (Deportment of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Park, Tae-Im (Departments of Physiology, College of Medicine, Yeungnam University) ;
  • Kim, Jong-Yeon (Departments of Physiology, College of Medicine, Yeungnam University) ;
  • Kim, Yong-Woon (Departments of Physiology, College of Medicine, Yeungnam University) ;
  • Lee, Dong-Chul (Departments of Orthopedic Surgery, College of Medicine, Yeungnam University) ;
  • Lee, Suck-Kang (Departments of Physiology, College of Medicine, Yeungnam University)
  • Published : 2005.06.21
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Abstract

The aim of the present study was to determine whether serotonergic drugs could reverse lipopolysaccharide (LPS)-induced anorexia in rats. LPS ($500{\mu}g$/kg body weight) and all serotonergic drugs, except for 8-OH-DPAT (subcutaneous), were injected intraperitoneally into Sprague-Dawley rats. Without the LPS injection, 8-OH-DPAT (1A agonist), metergoline (1/2 antagonist), and mianserin (2A/2C antagonist) exerted no effects on food intake at any of the doses tested, but ketanserin (2A antagonist) caused an increase of food intake at 4 mg/kg. RS-102221 (2C antagonist) reduced food intake at 2 and 4 mg/kg. LPS reduced food intake 1 hour after injection, and food intake remained low until the end of measurement period (24 hours) (p<0.05). Pretreatment of rats with 8-OH-DPAT partially recovered of cumulative food intake at all measured times (2, 4, 6, 8, and 24 hours after LPS injection). Pretreatment with metergoline resulted in a partial recovery of cumulative food intake at 2, 4, 6, and 8 hours, but not at 24 hours. Ketanserin caused partial recovery at 2 and 4 hours only. Mianserin and RS-102221 had no effects on LPS-reduced food intake. A variety of serotonergic drugs ameliorated anorexic symptoms, which suggesting that the serotonin system plays a role in LPS-induced anorexia.

Keywords

References

  1. Bendotti C, Samanin R. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT elicits eating in free-feeding rats by acting on central serotonin neurons. Eur J Pharmacol 121: 147-150, 1986 https://doi.org/10.1016/0014-2999(86)90405-X
  2. Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM. RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology 36: 621-629, 1997 https://doi.org/10.1016/S0028-3908(97)00049-X
  3. Choi SH, Kwon BS, Lee S, Houpt TA, Lee HT, Kim DG, Jahng JW. Systemic 5-hydroxy-L-tryptophan down-regulates the arcuate CART mRNA level in rats. Regul Pept 115: 73-80, 2003 https://doi.org/10.1016/S0167-0115(03)00126-5
  4. Cooney RN, Kimball SR, Vary TC. Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators. Shock 7: 1-16, 1997 https://doi.org/10.1097/00024382-199701000-00001
  5. Dunn AJ. Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparison with interleukin-1. J Pharmacol Exp Ther 261: 964-969, 1992
  6. Fantino M, Wieteska L. Evidence for a direct central anorectic effect of tumor-necrosis-factor-alpha in the rat. Physiol Behav 53: 477-483, 1993 https://doi.org/10.1016/0031-9384(93)90141-2
  7. Gardier AM, Malagie I, Trillat AC, Jacquot C, Artigas F. Role of 5-HT1A autoreceptors in the mechanism of action of serotoninergic antidepressant drugs: recent findings from in vivo microdialysis studies. Fundam Clin Pharmacol 10: 16-27, 1996. https://doi.org/10.1111/j.1472-8206.1996.tb00145.x
  8. Grignaschi G, Sironi F, Samanin R. Stimulation of 5-HT2A receptors in the paraventricular hypothalamus attenuates neuropeptide Y-induced hyperphagia through activation of corticotropin releasing factor. Brain Res 708: 173-176, 1996 https://doi.org/10.1016/0006-8993(95)01373-3
  9. Grunfeld C, Feingold KR. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. N Engl J Med 327: 329-337, 1992 https://doi.org/10.1056/NEJM199207303270506
  10. Grunfeld C, Pang M, Shimizu L, Shigenaga JK, Jensen P, Feingold KR. Resting energy expenditure, caloric intake, and short-term weight change in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Am J Clin Nutr 55: 455-460, 1992 https://doi.org/10.1093/ajcn/55.2.455
  11. Hewson G, Leighton GE, Hill RG, Hughes J. Ketanserin antagonises the anorectic effect of DL-fenfluramine in the rat. Eur J Pharmacol 145: 227-230, 1988 https://doi.org/10.1016/0014-2999(88)90236-1
  12. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev 46: 157-203, 1994
  13. Hrupka BJ, Langhans W. A role for serotonin in lipopolysaccharideinduced anorexia in rats. Pharmacol Biochem Behav 68: 355- 362, 2001 https://doi.org/10.1016/S0091-3057(00)00463-9
  14. Kent S, Bluthe RM, Dantzer R, Hardwick AJ, Kelley KWR, Rothwell NJ, Vannice JL. Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1. Proc Natl Acad Sci USA 89: 9117-9120, 1992a https://doi.org/10.1073/pnas.89.19.9117
  15. Kent S, Bluthe RM, Kelley KW, Dantzer R. Sickness behavior as a new target for drug development. Trends Pharmacol 13: 24-28, 1992b https://doi.org/10.1016/0165-6147(92)90012-U
  16. Lavicky J, Dunn AJ. Endotoxin administration stimulates cerebral catecholamine release in freely moving rats as assessed by microdialysis. J Neurosci Res 40: 407-413, 1995 https://doi.org/10.1002/jnr.490400316
  17. Lee MD, Clifton PG. Partial reversal of fluoxetine anorexia by the 5-HT antagonist metergoline. Psychopharmacology (Berl) 107: 359-364, 1992 https://doi.org/10.1007/BF02245162
  18. Leibowitz SF, Weiss GH, Shor-Posner G. Hypothalamic serotonin: pharmacological, biochemical, and behavioral analysis of its feeding-suppressive action. Clin Neuropharmacol 11: S51-S71, 1988
  19. Lenczowski MJ, Van Dam AM, Poole S, Larrick JW, Tilders FJ. Role of circulating endotoxin and interleukin-6 in the ACTH and corticosterone response to intraperitoneal LPS. Am J Physiol 273: R1870-1877, 1997
  20. Macallan G, Noble C, Baldwin C, Jebb SA, Prentice AM, Coward WA, Sawyer MB, McManus TJ, Griffin GE. Energy expenditure and wasting in human immunodeficiency virus infection. N Engl J Med 333: 83-88, 1995 https://doi.org/10.1056/NEJM199507133330202
  21. McCarthy DO. Tumor necrosis factor alpha and interleukin-6 have differential effects on food intake and gastric emptying in fasted rats. Res Nurs Health 23: 222-228, 2000 https://doi.org/10.1002/1098-240X(200006)23:3<222::AID-NUR6>3.0.CO;2-3
  22. McCarthy DO, Kluger MJ, Vander AJ. The role of fever in appetite suppression after endotoxin administration. Am J Clin Nutr 40: 310-316, 1984 https://doi.org/10.1093/ajcn/40.2.310
  23. Movat HZ, Cybulsky MI, Colditz IG, Chan MK, Dinarello CA. Acute inflammation in gram-negative infection: endotoxin, interleukin 1, tumor necrosis factor, and neutrophils. Fed Proc 46: 97-104, 1987
  24. Park S, Harrold JA, Widdowson PS, Williams G. Increased binding at 5-HT(1A), 5-HT (1B), and 5-HT (2A) receptors and 5-HT transporters in diet-induced obese rats. Brain Res 847: 90-97, 1999 https://doi.org/10.1016/S0006-8993(99)02055-7
  25. Plata-Salaman CR, Borkoski JP. Chemokines/intercrines and central regulation of feeding. Am J Physiol 266(5 Pt 2): R1711- 1715, 1994
  26. Raghavendra V, Kulkarni SK. Melatonin reversal of DOI-induced hypophagia in rats; possible mechanism by suppressing 5-HT (2A) receptor-mediated activation of HPA axis. Brain Res 860: 112-118, 2000 https://doi.org/10.1016/S0006-8993(00)02031-X
  27. Sergeyev V, Broberger C, Hokfelt T. Effect of LPS administration on the expression of POMC, NPY, galanin, CART and MCH mRNAs in the rat hypothalamus. Brain Res Mol Brain Res 90: 93-100, 2001 https://doi.org/10.1016/S0169-328X(01)00088-2
  28. Sharp T, Hjorth S. Application of brain microdialysis to study the pharmacology of the 5-HT1A autoreceptor. J Neurosci Methods 34: 83-90, 1990 https://doi.org/10.1016/0165-0270(90)90045-H
  29. Simansky KJ, Dave KD, Inemer BR, Nicklous DM, Padron JM, Aloyo VJ, Romano AG. A 5-HT2C agonist elicits hyperactivity and oral dyskinesia with hypophagia in rabbits. Physiol Behav 82: 97-107, 2004 https://doi.org/10.1016/j.physbeh.2004.04.028
  30. Simansky KJ, Nicklous DM. Parabrachial infusion of D-fenfluramine reduces food intake. Blockade by the 5-HT (1B) antagonist SB-216641. Pharmacol Biochem Behav 71: 681-690, 2002 https://doi.org/10.1016/S0091-3057(01)00740-7
  31. Simansky KJ, Sisk FC, Vaidya AH, Eberle-Wang K. Peripherally administered alpha-methyl-5-hydroxy-tryptamine and 5-carboxamidotryptamine reduce food intake via different mechanisms in rats. Behav Pharmacol 1: 241-246, 1989
  32. Simons JP, Schols AM, Buurman WA, Wouters EF. Weight loss and low body cell mass in males with lung cancer: relationship with systemic inflammation, acute-phase response, resting energy expenditure, and catabolic and anabolic hormones. Clin Sci 97: 215-223, 1999 https://doi.org/10.1042/CS19990021
  33. Sugimoto Y, Yamada J, Yoshikawa T, Horisaka K. The involvement of 5-HT1B receptors in the inhibitory effects of nitric oxide synthase inhibitor on 2-deoxy-D-glucose-induced hyperphagia in rats. Neuroreport 8: 2735-2737, 1997 https://doi.org/10.1097/00001756-199708180-00018
  34. Sugimoto Y, Yoshikawa T, Yamada J. Effects of peripheral administration of 5-hydroxytryptamine (5-HT) on 2-deoxy-D-glucoseinduced hyperphagia in rats. Biol Pharm Bull 25: 1364-1366, 2002 https://doi.org/10.1248/bpb.25.1364
  35. von Meyenburg C, Langhans W, Hrupka BJ. Evidence for a role of the 5-HT2C receptor in central lipopolysaccharide-, interleukin- 1 beta-, and leptin-induced anorexia. Pharmacol Biochem Behav 74: 1025-1031, 2003 https://doi.org/10.1016/S0091-3057(03)00030-3