Nelumbinis Semen Reverses a Decrease in $5-HT_{1A}$Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

  • Jang, Choon-Gon (Department of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Kang, Moon-Kyu (Purimed R&D Institute , Kyunghee University) ;
  • Cho, Jae-Han (Department of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Lee, Sun-Bok (Department of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Kim, Hyun-Taek (Department of Psychology, Korea University) ;
  • Park, Soon-Kwon (Department of Anatomy, Korea University College of Medicine) ;
  • Lee, Jin-Woo (College of Oriental Medicine, Kyunghee University) ;
  • Park, Seong-Kyu (College of Oriental Medicine, Kyunghee University) ;
  • Hong, Moo-Chang (College of Oriental Medicine, Kyunghee University) ;
  • Shin, Min-Kyu (College of Oriental Medicine, Kyunghee University) ;
  • Shim, In-Sup (East-West Medicine Research Institute , Kyunghee University) ;
  • Bae , Hyun-Su (Purimed R&D Institute , Kyunghee University, College of Oriental Medicine, Kyunghee University)
  • 발행 : 2004.01.01

초록

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

키워드

참고문헌

  1. Ase, A. R., Amdiss, F., Hebert, C., Huang, N., van Gelder, N. M., and Reader, T. A., Effects of antipsychotic drugs on dopamine and serotonin contents and metabolites, dopamine and serotonin transporters, and serotonin1A receptors. J. Neural Transm, 106,75-105 (1999) https://doi.org/10.1007/s007020050142
  2. Banasr, M., Hery, M., Printemps, R., and Daszuta, A., Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology, 29, 450-460 (2004) https://doi.org/10.1038/sj.npp.1300320
  3. Bench, C. J., Friston, K. J., Brown, R. G., Scott, L. C., Frackowiak, R. S., and Dolan, R. J., The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression. Psychol. Med., 22, 607-615 (1992) https://doi.org/10.1017/S003329170003806X
  4. Buhot, M. C., Martin, S., and Segu, L., Role of serotonin in memory impairment. Ann. Med., 32, 210-221 (2000) https://doi.org/10.3109/07853890008998828
  5. Butterweck, V., Jurgenliemk, G., Nahrstedt, A., and Winterhoff, H., Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta. Med., 66, 3-6 (2000) https://doi.org/10.1055/s-2000-11119
  6. Butterweck, V., Wall, A, Lieflander-Wulf, U., Winterhoff, H., and Nahrstedt, A, Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity. Pharmacopsychiatry, 30 Suppl2, 117-124 (1997). https://doi.org/10.1055/s-2007-979531
  7. Celada, P., Puig, M., Amargos-Bosch, M., Adell, A., and Artigas, F., The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J. Psychiatry Neurosci, 29, 252-265 (2004)
  8. Devanand, D. P., Pelton, G. H., Marston, K., Camacho, Y., Roose, S. P, Stern, Y, and Sackeim, H. A., Sertraline treatment of elderly patients with depression and cognitive impairment. Int. J. Geriatr Psychiatry, 18, 123-130 (2003) https://doi.org/10.1002/gps.802
  9. Dremencov, E., Gur, E., Lerer, B., and Newman, M. E., Effects of chronic antidepressants and electroconvulsive shock on serotonergic neurotransmission in the rat hippocampus. Prog. Neuropsychopharmacol. Biol. Psychiatry, 27, 729-739 (2003) https://doi.org/10.1016/S0278-5846(03)00123-4
  10. Drevets, W. C., Frank, E., Price, J. C., Kupfer, D. J., Greer, P. J., and Mathis, C., Serotonin type-1A receptor imaging in depression. Nucl. Med. Biol., 27, 499-507 (2000). https://doi.org/10.1016/S0969-8051(00)00119-0
  11. Drevets, W. C., Frank, E., Price, J. C., Kupfer, D. J., Holt, D., Greer, P. J., Huang, Y., Gautier, C., and Mathis, C., PET imaging of serotonin 1A receptor binding in depression. Biol. Psychiatry, 46,1375-1387 (1999) https://doi.org/10.1016/S0006-3223(99)00189-4
  12. Elena Castro, M., Diaz, A., del Olmo, E., and Pazos, A., Chronic fluoxetine induces opposite changes in G protein coupling at pre and postsynaptic 5-HT1A receptors in rat brain. Neuropharmacology, 44, 93-101 (2003) https://doi.org/10.1016/S0028-3908(02)00340-4
  13. Haddjeri, N., Blier, P., and de Montigny, C., Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors. J. Neurosci., 18, 10150-10156 (1998)
  14. Hasrat, J. A., De Bruyne, T., De Backer, J. P., Vauquelin, G., and Vlietinck, A. J., Isoquinoline derivatives isolated from the fruit of Annona muricata as 5-HTergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products. J. Pharm. Pharmacol., 49,1145-1149 (1997) https://doi.org/10.1111/j.2042-7158.1997.tb06058.x
  15. Katz, R. J., Animal models and human depressive disorders. Neurosci. Biobehav. Rev., 5, 231-246 (1981) https://doi.org/10.1016/0149-7634(81)90004-X
  16. Katz, R. J., Animal model of depression: pharmacological sensitivity of a hedonic deficit. Pharmacol. Biochem. Behav., 16,965-968 (1982) https://doi.org/10.1016/0091-3057(82)90053-3
  17. Keck, B. J. and Lakoski, J. M., Region-specific serotonin1A receptor turnover following irreversible blockade with EEDQ. Neuroreport, 7, 2717-2721 (1996) https://doi.org/10.1097/00001756-199611040-00062
  18. Khalifa, A. E., Hypericum pertoratum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice. J. Ethnopharmacol., 76, 49-57 (2001) https://doi.org/10.1016/S0378-8741(01)00210-0
  19. Kline, A. E., Yu, J., Horvath, E., Marion, D. W., and Dixon, C. E., The selective 5-HT(1A) receptor agonist repinotan HCI attenuates histopathology and spatial learning deficits following traumatic brain injury in rats. Neuroscience, 106, 547-555 (2001) https://doi.org/10.1016/S0306-4522(01)00300-1
  20. Leitch, M. M., Ingram, C. D., Young, A. H., McQuade, R., and Gartside, S. E., Flattening the corticosterone rhythm attenuates 5-HT1A autoreceptor function in the rat: relevance for depression. Neuropsychopharmacology, 28, 119-125 (2003) https://doi.org/10.1038/sj.npp.1300016
  21. Leonard, B. E., Pharmacological differences of serotonin reuptake inhibitors and possible clinical relevance. Drugs, 43 Suppl2, 3-9; discussion 9-10 (1992)
  22. Li, G. R., Li, X. G., and Lu, F. H., Effects of neferine on transmembrane potentials of guinea pig myocardium. Zhongguo Yao Li Xue Bao, 10, 406-410 (1989)
  23. Li, G. R., Qian, J. Q., and Lu, F. H., Effects of neferine on heart electromechanical activity in anaesthetized cats. Zhongguo Yao Li Xue Bao, 11, 158-161 (1990)
  24. Lozoya, X., Meckes, M., Abou-Zaid, M., Tortoriello, J., Nozzolillo, C., and Amason, J. T., Quercetin glycosides in Psidium guajava L. leaves and determination of a spasmolytic principle. Arch. Med. Res., 25,11-15 (1994)
  25. MacQueen, G. M., Campbell, S., McEwen, B. S., Macdonald, K., Amano, S., Joffe, R. T., Nahmias, C., and Young, L. T., Course of illness, hippocampal function, and hippocampal volume in major depression. Proc. Natl. Acad. Sci. U.S.A., 100,1387-1392 (2003) https://doi.org/10.1073/pnas.0337481100
  26. Monleon, S., D'Aquila, P., Parra, A., Simon, V. M., Brain, P. F., and Willner, P., Attenuation of sucrose consumption in mice by chronic mild stress and its restoration by imipramine. Psychopharmacology (Berl), 117,453-457 (1995) https://doi.org/10.1007/BF02246218
  27. Muller, W. E., Rolli, M., Schafer, C., and Hafner, U., Effects of hypericum extract (Ll 160) in biochemical models of antidepressant activity. Pharmacopsychiatry, 30 Suppl 2, 102-107 (1997) https://doi.org/10.1055/s-2007-979528
  28. Muscat, R., Papp, M., and Willner, P., Reversal of stressinduced anhedonia by the atypical antidepressants, fluoxetine and maprotiline. Psychopharmacology (Berl), 109, 433-438 (1992) https://doi.org/10.1007/BF02247719
  29. Nieto-Sampedro, M., Shelton, D., and Cotman, C. W., Specific binding of kainic acid to purified subcellular fractions from rat brain. Neurochem. Res., 5, 591-604 (1980) https://doi.org/10.1007/BF00964781
  30. Nowak, G., Szewczyk, B., Wieronska, J. M., Branski, P., Palucha, A., Pile, A., Sadlik, K., and Piekoszewski, W, Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats. Brain Res. Bull., 61, 159-164 (2003) https://doi.org/10.1016/S0361-9230(03)00104-7
  31. Papp, M., Willner, P., and Muscat, R., An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress. Psychopharmacology (Berl), 104, 255-259 (1991) https://doi.org/10.1007/BF02244188
  32. Protais, P., Arbaoui, J., Bakkali, E. H., Bermejo, A., and Cortes, D., Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes. J. Nat. Prod., 58, 1475-1484 (1995) https://doi.org/10.1021/np50124a001
  33. Radja, F., Descarries, L., Dewar, K. M., and Reader, T. A., Serotonin 5-HT1 and 5-HT2 receptors in adult rat brain after neonatal destruction of nigrostriatal dopamine neurons: a quantitative autoradiographic study. Brain Res., 606, 273-285 (1993) https://doi.org/10.1016/0006-8993(93)90995-Y
  34. Sargent, P. A., Kjaer, K. H., Bench, C. J., Rabiner, E. A., Messa, C., Meyer, J., Gunn, R. N., Grasby, P. M., and Cowen, P. J., Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch. Gen. Psychiatry, 57, 174-180 (2000) https://doi.org/10.1001/archpsyc.57.2.174
  35. Shoji, N., Umeyama, A., Saito, N., luchi, A., Takemoto, T., Kajiwara, A., and Ohizumi, Y., Asimilobine and lirinidine, serotonergic receptor antagonists, from Nelumbo nucifera. J. Nat. Prod., 50, 773-774 (1987) https://doi.org/10.1021/np50052a044
  36. Soares, J. C. and Mann, J. J., The functional neuroanatomy of mood disorders. J. Psychiatr Res., 31,393-432 (1997) https://doi.org/10.1016/S0022-3956(97)00016-2
  37. Sohn, D. H., Kim, Y. C., Oh, S. H., Park, E. J., Li, X,, and Lee, B. H., Hepatoprotective and free radical scavenging effects of Nelumbo nucifera. Phytomedicine, 10, 165-169 (2003) https://doi.org/10.1078/094471103321659889
  38. Wang, J., Hu, X., Yin, W, and Cai, H., Alkaloids of plumula Nelumbinis. Zhongguo Zhong Yao Za Zhi, 16, 673-675, 703, (1991)
  39. Willner, P., The validity of animal models of depression. Psychopharmacology (Berl), 83,1-16 (1984) https://doi.org/10.1007/BF00427414
  40. Willner, P., Animal models as simulations of depression. Trends Pharmacol. Sci., 12, 131-136 (1991) https://doi.org/10.1016/0165-6147(91)90529-2
  41. Willner, P., The mesolimbic dopamine system as a target for rapid antidepressant action. Int. Clin. Psychopharmacol, 12 Suppl3, S7-14 (1997a). https://doi.org/10.1002/(SICI)1099-1077(199706)12:1+3.0.CO;2-B
  42. Willner, P., Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl), 134,319-329 (1997b) https://doi.org/10.1007/s002130050456
  43. Willner, P., Moreau, J. L., Nielsen, C. K., Papp, M., and Sluzewska, A., Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight. Physiol. Behav., 60, 129-134 (1996) https://doi.org/10.1016/0031-9384(95)02256-2
  44. Willner, P, Towell, A., Sampson, D., Sophokleous, S., and Muscat, R., Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl), 93, 358-364 (1987)
  45. Zacharko, R. M., Bowers, W. J., and Anisman, H., Responding for brain stimulation: stress and desmethylimipramine. Prog. Neuropsychopharmacol. Biol. Psychiatry, 8, 601-606 (1984)
  46. Zacharko, R. M., Bowers, W. J., Kokkinidis, L., and Anisman, H., Region-specific reductions of intracranial self-stimulation after uncontrollable stress: possible effects on reward processes. Behav. Brain Res., 9,129-141 (1983) https://doi.org/10.1016/0166-4328(83)90123-7
  47. Zelenski, S. G., Alkaloids of Nelumbo lutea (Wild.) pers. (Nymphaeaceae). J. Pharm. Sci., 66, 1627-1628 (1977) https://doi.org/10.1002/jps.2600661132