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.
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References
Brown ES, Chandler PA. Mood and cognitive changes during systemic corticosteroid therapy. Prim Care Companion J Clin Psychiatry 2001, 3: 17–21.
Belanoff JK, Gross K, Yager A, Schatzberg AF. Corticosteroids and cognition. J Psychiatr Res 2001, 35: 127–145.
Starkman MN, Schteingart DE. Neuropsychiatric manifestations of patients with Cushing’s syndrome. Relationship to cortisol and adrenocorticotropic hormone levels. Arch Intern Med 1981, 141: 215–219.
Bisagno V, Ferrini M, Rios H, Zieher LM, Wikinski SI. Chronic corticosterone impairs inhibitory avoidance in rats: possible link with atrophy of hippocampal CA3 neurons. Pharmacol Biochem Behav 2000, 66: 235–240.
Magarinos AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience 1995, 69: 89–98.
Cameron HA, Gould E. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 1994, 61: 203–209.
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.
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.
Malberg JE. Implications of adult hippocampal neurogenesis in antidepressant action. J Psychiatry Neurosci 2004, 29: 196–205.
Hellsten J, Wennstrom M, Mohapel P, Ekdahl CT, Bengzon J, Tingstrom A. Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment. Eur J Neurosci 2002, 16: 283–290.
Sapolsky RM. Glucocorticoid toxicity in the hippocampus: temporal aspects of neuronal vulnerability. Brain Res 1985, 359: 300–305.
Mirescu C, Peters JD, Gould E. Early life experience alters response of adult neurogenesis to stress. Nat Neurosci 2004, 7: 841–846.
Jacobs BL, Tanapat P, Reeves AJ, 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.
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.
Neumaier JF, Sexton TJ, Hamblin MW, Beck SG. Corticosteroids regulate 5-HT1A but not 5-HT1B receptor mRNA in rat hippocampus. Brain Res Mol Brain Res 2000, 82: 65–73.
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.
Cameron HA, 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.
Coppell AL, Pei Q, Zetterstrom TS. Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology 2003, 44: 903–910.
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.
Nakagawa S, Kim JE, 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.
Geuze E, Vermetten E, Bremner JD. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol Psychiatry 2005, 10: 160–184
Vythilingam M, Vermetten E, Anderson GM, Luckenbaugh D, Anderson ER, Snow J, et al. Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiatry 2004, 56: 101–112.
Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med 2006, 3: e343.
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Qiu, G., Helmeste, D.M., Samaranayake, A.N. et al. Modulation of the suppressive effect of corticosterone on adult rat hippocampal cell proliferation by paroxetine. Neurosci. Bull. 23, 131–135 (2007). https://doi.org/10.1007/s12264-007-0019-9
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DOI: https://doi.org/10.1007/s12264-007-0019-9