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. 2008 Feb 3;23(3):131–135. doi: 10.1007/s12264-007-0019-9

Modulation of the suppressive effect of corticosterone on adult rat hippocampal cell proliferation by paroxetine

Guang Qiu 1, Daiga M Helmeste 2, Asanka N Samaranayake 1, Wui-Man Lau 4, Tatia M C Lee 3, Siu-Wa Tang 2,4,✉, Kwok-Fai So 1,✉
PMCID: PMC5550626  PMID: 17612590

Abstract

Objective

The literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study.

Methods

Adult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry.

Results

The corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation.

Conclusion

This may have clinic application in preventing hippocampal damage after glucocorticoid treatment.

Keywords: paroxetine, bromodeoxyuridine, corticosterone, hippocampus, cell proliferation, neurogenesis

Contributor Information

Siu-Wa Tang, Phone: 852-28554486, Email: mswtang@hkucc.hku.hk.

Kwok-Fai So, Phone: 852-28199216, FAX: 852-28176821, Email: hrmaskf@hkucc.hku.hk.

References

  • [1].Brown E.S., Chandler P.A. Mood and cognitive changes during systemic corticosteroid therapy. Prim Care Companion J Clin Psychiatry. 2001;3:17–21. doi: 10.4088/pcc.v03n0104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2].Belanoff J.K., Gross K., Yager A., Schatzberg A.F. Corticosteroids and cognition. J Psychiatr Res. 2001;35:127–145. doi: 10.1016/S0022-3956(01)00018-8. [DOI] [PubMed] [Google Scholar]
  • [3].Starkman M.N., Schteingart D.E. Neuropsychiatric manifestations of patients with Cushing’s syndrome. Relationship to cortisol and adrenocorticotropic hormone levels. Arch Intern Med. 1981;141:215–219. doi: 10.1001/archinte.141.2.215. [DOI] [PubMed] [Google Scholar]
  • [4].Bisagno V., Ferrini M., Rios H., Zieher L.M., Wikinski S.I. Chronic corticosterone impairs inhibitory avoidance in rats: possible link with atrophy of hippocampal CA3 neurons. Pharmacol Biochem Behav. 2000;66:235–240. doi: 10.1016/S0091-3057(00)00265-3. [DOI] [PubMed] [Google Scholar]
  • [5].Magarinos A.M., McEwen B.S. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience. 1995;69:89–98. doi: 10.1016/0306-4522(95)00259-L. [DOI] [PubMed] [Google Scholar]
  • [6].Cameron H.A., Gould E. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience. 1994;61:203–209. doi: 10.1016/0306-4522(94)90224-0. [DOI] [PubMed] [Google Scholar]
  • [7].Bruel-Jungerman E., Laroche S., Rampon C. New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. Eur J Neurosci. 2005;21:513–521. doi: 10.1111/j.1460-9568.2005.03875.x. [DOI] [PubMed] [Google Scholar]
  • [8].Santarelli L., Saxe M., Gross C., Surget A., Battaglia F., Dulawa S., et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805–809. doi: 10.1126/science.1083328. [DOI] [PubMed] [Google Scholar]
  • [9].Malberg J.E. Implications of adult hippocampal neurogenesis in antidepressant action. J Psychiatry Neurosci. 2004;29:196–205. [PMC free article] [PubMed] [Google Scholar]
  • [10].Hellsten J., Wennstrom M., Mohapel P., Ekdahl C.T., Bengzon J., Tingstrom A. Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment. Eur J Neurosci. 2002;16:283–290. doi: 10.1046/j.1460-9568.2002.02093.x. [DOI] [PubMed] [Google Scholar]
  • [11].Sapolsky R.M. Glucocorticoid toxicity in the hippocampus: temporal aspects of neuronal vulnerability. Brain Res. 1985;359:300–305. doi: 10.1016/0006-8993(85)91440-4. [DOI] [PubMed] [Google Scholar]
  • [12].Mirescu C., Peters J.D., Gould E. Early life experience alters response of adult neurogenesis to stress. Nat Neurosci. 2004;7:841–846. doi: 10.1038/nn1290. [DOI] [PubMed] [Google Scholar]
  • [13].Jacobs B.L., Tanapat P., Reeves A.J., Gould E. Serotonin stimulates the production of new hippocampal granule neurons via the 5-HT1A receptor in the adult rat. Soc Neurosci Abstr. 1998;24:1992. [Google Scholar]
  • [14].Banasr M., Hery M., Printemps R., Daszuta A. Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology. 2004;29:450–460. doi: 10.1038/sj.npp.1300320. [DOI] [PubMed] [Google Scholar]
  • [15].Neumaier J.F., Sexton T.J., Hamblin M.W., Beck S.G. Corticosteroids regulate 5-HT1A but not 5-HT1B receptor mRNA in rat hippocampus. Brain Res Mol Brain Res. 2000;82:65–73. doi: 10.1016/S0169-328X(00)00181-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16].Czyrak A., Mackowiak M., Chocyk A., Fijal K., Tokarski K., Bijak M., et al. Prolonged corticosterone treatment alters the responsiveness of 5-HT1A receptors to 8-OH-DPAT in rat CA1 hippocampal neurons. Naunyn Schmiedebergs Arch Pharmacol. 2002;366:357–367. doi: 10.1007/s00210-002-0586-2. [DOI] [PubMed] [Google Scholar]
  • [17].Cameron H.A., Tanapat P., Gould E. Adrenal steroids and Nmethyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway. Neuroscience. 1998;82:349–354. doi: 10.1016/S0306-4522(97)00303-5. [DOI] [PubMed] [Google Scholar]
  • [18].Coppell A.L., Pei Q., Zetterstrom T.S. Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology. 2003;44:903–910. doi: 10.1016/S0028-3908(03)00077-7. [DOI] [PubMed] [Google Scholar]
  • [19].Hashimoto K., Shimizu E., Iyo M. Critical role of brain-derived neurotrophic factor in mood disorders. Brain Res Brain Res Rev. 2004;45:104–114. doi: 10.1016/j.brainresrev.2004.02.003. [DOI] [PubMed] [Google Scholar]
  • [20].Nakagawa S., Kim J.E., Lee R., Chen J., Fujioka T., Malberg J., et al. Localization of phosphorylated cAMP response elementbinding protein in immature neurons of adult hippocampus. J Neurosci. 2002;22:9868–9876. doi: 10.1523/JNEUROSCI.22-22-09868.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Geuze E., Vermetten E., Bremner J.D. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol Psychiatry. 2005;10:160–184. doi: 10.1038/sj.mp.4001579. [DOI] [PubMed] [Google Scholar]
  • [22].Vythilingam M., Vermetten E., Anderson G.M., Luckenbaugh D., Anderson E.R., Snow J., et al. Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiatry. 2004;56:101–112. doi: 10.1016/j.biopsych.2004.04.002. [DOI] [PubMed] [Google Scholar]
  • [23].Stockman L.J., Bellamy R., Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3:e343. doi: 10.1371/journal.pmed.0030343. [DOI] [PMC free article] [PubMed] [Google Scholar]

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