Sex Differences in the Effects of Sertraline and Stressors in Rats Previously Exposed to Restraint Stress

DOI: 10.4236/jbise.2015.87038   PDF   HTML   XML   3,016 Downloads   3,570 Views   Citations


The serotonergic system in the brain plays a major role in mood and anxiety regulation when exposed to stress. The aim of the present study was to evaluate the effects of Sertraline administration in coping with stress using the behavioural paradigms of the acoustic startle reflex (ASR) and its prepulse inhibition (PPI) in both sexes. Wistar rats were divided into two groups: intact animals and exposed to restraint stress (RS) 3 times per day during 7 days, which were then subdivided into three other groups: injected with Sertraline (5 mg/kg/day) or the drug vehicle saline for 8 consecutive days, and non-injected. ASR and PPI values were analyzed along 4 sessions to determine behavioral changes. Upon it, we also determine the effects of acute immobilization stress analyzing physiological stress indicators in blood. Our data show sex differences in response to stress paradigms. RS affected more intensely males than females, disturbing the males’ growth and the long-term startle habituation that were not affected in females. PPI increased in the vehicle-injected animals when compared to baseline in both sexes, and Sertraline reversed more efficiently it in females. Moreover, despite both sexes exposed to stressful paradigms exhibited a significant increase in serum glutamic-oxaloacetic transaminase and lactate dehydrogenase enzymes when compared with intact controls, as well as leucopenia, some differences according to sex were found in the haemostatic response to stress. Notably, the repeated injections procedure disturbed the early response to stress, which Sertraline only attenuated in both sexes. Our data suggest that 8-day Sertraline administration is effective in reversing stress-induced changes in some physio-logical parameters, but insufficient to return immunological values to normality.

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Pereira-Figueiredo, I. , Carro, J. , Muñoz, L. , Sancho, C. , Castellano, O. , Gómez-Nieto, R. and López, D. (2015) Sex Differences in the Effects of Sertraline and Stressors in Rats Previously Exposed to Restraint Stress. Journal of Biomedical Science and Engineering, 8, 399-419. doi: 10.4236/jbise.2015.87038.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] McEwen, B.S. (2008) Central Effects of Stress Hormones in Health and Disease: Understanding the Protective and Damaging Effects of Stress and Stress Mediators. European Journal of Pharmacology, 583, 174-185.
[2] von Kanel, R., Kudielka, B.M., Haeberli, A., Stutz M., Fischer, J.E. and Patterson, S.M. (2009) Prothrombotic Changes with Acute Psychological Stress: Combined Effect of Hemoconcentration and Genuine Coagulation Activation. Thrombosis Research, 123, 622-630.
[3] Cox, B.M., Alsawah, F., McNeill, P.C., Galloway, M.P. and Perrine, S.A. (2011) Neurochemical, Hormonal, and Behavioral Effects of Chronic Unpredictable Stress in the Rat. Behavioural Brain Research, 220, 106-111.
[4] Swaab, D.F., Bao, A.-M. and Lucassen, P.J. (2005) The Stress System in the Human Brain in Depression and Neurodegeneration. Ageing Research Reviews, 4, 141-194.
[5] Black, P.H. and Garbutt, D. (2002) Stress, Inflammation and Cardiovascular Disease. Journal of Psychosomatic Research, 52, 1-23.
[6] Bai, Y.-M., Su, T.-P., Chen, M.-H., Chen, T.-J. and Chang, W.-H. (2013) Risk of Developing Diabetes Mellitus and Hyperlipidemia among Patients with Bipolar Disorder, Major Depressive Disorder, and Schizophrenia: A 10-Year Nationwide Population-Based Prospective Cohort Study. Journal of Affective Disorders, 150, 57-62.
[7] Bierhaus, A., Humpert, P.M. and Nawroth, P.P. (2006) Linking Stress to Inflammation. Anesthesiology Clinics of North America, 24, 325-340.
[8] de Kloet, E.R., Joels, M. and Holsboer, F. (2005) Stress and the Brain: From Adaptation to Disease. Nature Reviews Neuroscience, 6, 463-475.
[9] Leonard, B.E. (2005) The HPA and Immune Axes in Stress: The Involvement of the Serotonergic System. European Psychiatry, 20, S302-S306.
[10] Grissom, N. and Bhatnagar, S. (2009) Habituation to Repeated Stress: Get Used to It. Neurobiology of Learning and Memory, 92, 215-224.
[11] Pilz, P.K.D. and Schnitzler, H.-U. (1996) Habituation and Sensitization of the Acoustic Startle Response in Rats: Amplitude, Threshold, and Latency Measures. Neurobiology of Learning and Memory, 66, 67-79.
[12] Hamer, M., Gibson, E.L., Vuononvirta, R., Williams, E. and Steptoe, A. (2006) Inflammatory and Hemostatic Responses to Repeated Mental Stress: Individual Stability and Habituation over Time. Brain, Behavior, and Immunity, 20, 456-459.
[13] Young, B.J., Helmstetter, F.J., Rabchenuk, S.A. and Leaton, R.N. (1991) Effects of Systemic and Intra-Amygdaloid Diazepam on Long-Term Habituation of Acoustic Startle in Rats. Pharmacology Biochemistry and Behavior, 39, 903- 909.
[14] Li, N., Ping, J., Wu, R., Wang, C., Wu, X. and Li, L. (2008) Auditory Fear Conditioning Modulates Prepulse Inhibition in Socially Reared Rats and Isolation-Reared Rats. Behavioral Neuroscience, 122, 107-118.
[15] Johansson, C., Jackson, D.M., Zhang, J. and Svensson, L. (1995) Prepulse Inhibition of Acoustic Startle, a Measure of Sensorimotor Gating: Effects of Antipsychotics and Other Agents in Rats. Pharmacology Biochemistry and Behavior, 52, 649-654.
[16] Van den Buuse, M. (2007) Pre-Pulse Inhibition. Encyclopedia of Stress. New York, Academic Press, 180-183.
[17] Braff, D.L., Geyer, M.A. and Swerdlow, N.R. (2001) Human Studies of Prepulse Inhibition of Startle: Normal Subjects, Patient Groups, and Pharmacological Studies. Psychopharmacology, 156, 234-258.
[18] Lehmann, J., Pryce, C.R. and Feldon, J. (1999) Sex Differences in the Acoustic Startle Response and Prepulse Inhibition in Wistar Rats. Behavioural Brain Research, 104, 113-117.
[19] Grillon, C. (2002) Startle Reactivity and Anxiety Disorders: Aversive Conditioning, Context, and Neurobiology. Biological Psychiatry, 52, 958-975.
[20] Geyer, M.A. (2006) The Family of Sensorimotor Gating Disorders: Comorbidities or Diagnostic Overlaps? Neurotoxicity Research, 10, 211-220.
[21] Ludewig, S., Ludewig, K., Geyer, M., Hell, D. and Vollenweider, F.X. (2001) Deficient Prepulse Inhibition of the Acoustic Startle Reflex in Panic Disorder. European Neuropsychopharmacology, 11, S312.
[22] Hoenig, K., Hochrein, A., Quednow, B.B., Maier, W. and Wagner, M. (2005) Impaired Prepulse Inhibition of Acoustic Startle in Obsessive-Compulsive Disorder. Biological Psychiatry, 57, 1153-1158.
[23] Meincke, U., Light, G.A., Geyer, M.A., Braff, D.L. and Gouzoulis-Mayfrank, E. (2004) Sensitization and Habituation of the Acoustic Startle Reflex in Patients with Schizophrenia. Psychiatry Research, 126, 51-61.
[24] Chen, Y., Mao, Y., Zhou, D., Hu, X., Wang, J. and Ma, Y. (2010) Environmental Enrichment and Chronic Restraint Stress in ICR Mice: Effects on Prepulse Inhibition of Startle and Y-Maze Spatial Recognition Memory. Behavioural Brain Research, 212, 49-55.
[25] Albonetti, M.E. and Farabollini, F. (1993) Effects of Single and Repeated Restraint on the Social Behavior of Male Rats. Physiology & Behavior, 53, 937-942.
[26] Vermetten, E. and Bremner, J.D. (2002) Circuits and Systems in Stress. I. Preclinical Studies. Depress Anxiety, 15, 126-147.
[27] Buynitsky, T. and Mostofsky, D.I. (2009) Restraint Stress in Biobehavioral Research: Recent Developments. Neuroscience Biobehavioral Reviews, 33, 1089-1098.
[28] Bowman, R.E., Micik, R., Gautreaux, C., Fernandez, L. and Luine, V.N. (2009) Sex-Dependent Changes in Anxiety, Memory, and Monoamines Following One Week of Stress. Physiology & Behavior, 97, 21-29.
[29] Giardino, L., Bettelli, C., Pozza, M. and Calzà, L. (1999) Regulation of CCK mRNA Expression in the Rat Brain by Stress and Treatment with Sertraline, a Selective Serotonin Re-Uptake Inhibitor. Brain Research, 824, 304-307.
[30] Ulloa, J.L., Castaneda, P., Berríos, C., Díaz-Veliz, G., Mora, S., Bravo, J.A., et al. (2010) Comparison of the Antidepressant Sertraline on Differential Depression-Like Behaviors Elicited by Restraint Stress and Repeated Corticosterone Administration. Pharmacology Biochemistry and Behavior, 97, 213-221.
[31] Azmitia, E.C. (2001) Modern Views on an Ancient Chemical: Sero-tonin Effect on Cell Proliferation, Maturation, and Apoptosis. Brain Research Bulletin, 56, 413-424.
[32] Lauder, J.M. (1990) Ontogeny of the Serotonergic System in the Rat: Serotonin as a Developmental Signal. Annals of the New York Academy of Sciences, 600, 297-313.
[33] Quednow, B.B., Kuhn K.-U., Mossner, R., Schwab, S.G., Schuhmacher, A., Maier, W., et al. (2008) Sensorimotor Gating of Schizophrenia Patients Is Influenced by 5-HT2A Receptor Polymorphisms. Biological Psychiatry, 64, 434- 437.
[34] Quednow, B.B, Kuhn, K.U., Stelzenmuelle, R., Hoenig, K., Maier, W. and Wagner, M. (2004) Effects of Serotonergic and Noradrenergic Antidepressants on Auditory Startle Response in Patients with Major Depression. Psychopharmacology, 175, 399-406.
[35] Pouzet, B., Andersen, M.P. and Hogg, S. (2005) Effects of Acute Treatment with Antidepressant Drugs on Sensorimotor Gating Deficits in Rats. Psychopharmacology, 178, 9-16.
[36] Brauer, D., Strobel, A., Hensch, T., Diers, K., Lesch, K.P. and Brocke, B. (2009) Genetic Variation of Serotonin Receptor Function Affects Prepulse Inhibition of the Startle. Journal of Neural Transmission, 116, 607-613.
[37] Raz, S. and Berger, B.D. (2010) Effects of Fluoxetine and PCPA on Isolation-Induced Morphine Self-Administration and Startle Reactivity. Pharmacology Biochemistry and Behavior, 96, 59-66.
[38] Calabrese, F., Molteni, R. and Riva, M.A. (2011) Antistress Properties of Antidepressant Drugs and Their Clinical Implications. Pharmacology & Therapeutics, 132, 39-56.
[39] Vaswani, M., Linda F.K. and Ramesh, S. (2003) Role of Selective Serotonin Reuptake Inhibitors in Psychiatric Disorders: A Comprehensive Review. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 27, 85-102.
[40] Siepmann, M., Grossmann, J., Muck-Weymann, M. and Kirch, W. (2003) Effects of Sertraline on Autonomic and Cognitive Functions in Healthy Volunteers. Psychopharmacology, 168, 293-298.
[41] González, B.G. and Escobar, A. (2002) Neuroanatomía del estrés. Revista Mexicana de Neurociencia, 3, 273-282.
[42] Faraday, M. (2002) Rat Sex and Strain Differences in Responses to Stress. Physiology & Behavior, 75, 507-522.
[43] Chadda, R. and Devaud, L.L. (2005) Differential Effects of Mild Repeated Restraint Stress on Behaviors and GABAA Receptors in Male and Female Rats. Pharmacology Biochemistry and Behavior, 81, 854-863.
[44] Maeng, L.Y. and Milad, M.R. (2015) Sex Differences in Anxiety Disorders: Interactions between Fear, Stress, and Gonadal Hormones. Hormones and Behavior (in Press).
[45] Elakovic, I, Brkljacic, J. and Matic, G. (2009) Gender-Related Differences in the Effects of Antidepressant Imipramine on Glucocorticoid Receptor Binding Properties and Association with Heat Shock Proteins in the Rat Liver and Kidney. European Journal of Pharmacology, 608, 7-13.
[46] Kornstein, S.G., Schatzberg, A.F., Thase, M.E., Yonkers, K.A., McCullough, J.P., Keitner, G.I., et al. (2000) Gender Differences in Treatment Response to Sertraline versus Imipramine in Chronic Depression. The American Journal of Psychiatry, 157, 1445-1452.
[47] Castellano, O., Moscoso, A., Riolobos, A.S., Carro, J., Arji, M., Molina, V., et al. (2009) Chronic Administration of Risperidone to Healthy Rats: A Behavioural and Morphological Study. Behavioural Brain Research, 205, 488-498.
[48] Adams, A.L., Hudson, A., Ryan, C.L. and Doucette, T.A. (2008) Effects of Estrous Stage and Time of Day on Prepulse Inhibition in Female Rats. Journal of Neuroscience Methods, 173, 295-298.
[49] Marcondes, F.K., Bianchi, F.J. and Tanno, A.P. (2002) Determination of the Estrous Cycle Phases of Rats: Some Helpful Considerations. Brazilian Journal of Biology, 62, 609-614.
[50] Pereira-Figueiredo, I., Sancho, C., Carro, J., Castellano, O. and López, D.E. (2014) The Effects of Sertraline Administration from Adolescence to Adulthood on Physiological and Emotional Development in Prenatally Stressed Rats of Both Sexes. Frontiers in Behavioral Neuroscience, 8, 260.
[51] Koenig, J.I., Elmer, G.I., Shepard, P.D., Lee, P.R., Mayo, C., Joy, B., et al. (2005) Prenatal Exposure to a Repeated Variable Stress Paradigm Elicits Behavioral and Neuroendocrinological Changes in the Adult Offspring: Potential Relevance to Schizophrenia. Behavioural Brain Research, 156, 251-261.
[52] Kjaer, S.L., Wegener, G., Rosenberg, R., Lund, S.P. and Hougaard, K.S. (2010) Prenatal and Adult Stress Interplay-Behavioral Implications. Brain Research, 1320, 106-113.
[53] Chung, S., Son, G.H., Park, S.H., Park, E., Lee, K.H., Geum, D., et al. (2005) Differential Adaptive Responses to Chronic Stress of Maternally Stressed Male Mice Offspring. Endocrinology, 146, 3202-3210.
[54] Santos, J.M., Martinez, R.C.R. and Brandao, M.L. (2006) Effects of Acute and Subchronic Treatments with Fluoxetine and Desipramine on the Memory of Fear in Moderate and High-Intensity Contextual Conditioning. European Journal of Pharmacology, 542, 121-128.
[55] Ishii, D., Matsuzawa, D., Fujita, Y., Sutoh, C., Ohtsuka, H., Matsuda, S., et al. (2010) Enhancement of Acoustic Prepulse Inhibition by Contextual Fear Conditioning in Mice Is Maintained Even after Contextual Fear Extinction. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34, 183-188.
[56] Pijlman, F.T.A., Herremans, A.H.J., van de Kieft, J., Kruse, C.G. and van Ree, J.M. (2003) Behavioural Changes after Different Stress Paradigms: Prepulse Inhibition Increased after Physical, but Not Emotional Stress. European Neuropsychopharmacology, 13, 369-380.
[57] Scholes, K.E. and Martin-Iverson, M.T. (2009) Relationships between Prepulse Inhibition and Cognition Are Mediated by Attentional Processes. Behavioural Brain Research, 205, 456-467.
[58] Foley, K.A., MacFabe, D.F., Kavaliers, M. and Ossenkopp, K.-P. (2015) Sexually Dimorphic Effects of Prenatal Exposure to Lipopolysaccharide, and Prenatal and Postnatal Exposure to Propionic Acid, on Acoustic Startle Response and Prepulse Inhibition in Adolescent Rats: Relevance to Autism Spectrum Disorders. Behavioural Brain Research, 278, 244-256.
[59] Conrad, C.D., Jackson, J.L., Wieczorek, L., Baran, S.E., Harman, J.S., Wright, R.L., et al. (2004) Acute Stress Impairs Spatial Memory in Male but Not Female Rats: Influence of Estrous Cycle. Pharmacology Biochemistry and Behavior, 78, 569-579.
[60] Cornwell, B.R., Echiverri, A.M., Covington, M.F. and Grillon, C. (2008) Modality-Specific Attention under Imminent but Not Remote Threat of Shock: Evidence from Differential Prepulse Inhibition of Startle. Psychological Science, 19, 615-622.
[61] Tang, A.C., Jiang, H., Yang, Z., Zhang, Y., Romeo, R.D. and McEwen, B.S. (2011) Converging Influence of Neonatal Novelty Experience and Maternal Self-Stress Regulation on the Plasticity of Offspring Acoustic Startle Response Latency. Behavioural Brain Research, 221, 253-260.
[62] Swerdlow, N.R., Hartman, P.L. and Auerbach, P.P. (1997) Changes in Sensorimotor Inhibition across the Menstrual Cycle: Implications for Neuropsychiatric Disorders. Biological Psychiatry, 41, 452-460.
[63] Ellenbroek, B.A., van den Kroonenberg, P.T.J.M. and Cools, A.R. (1998) The Effects of an Early Stressful Life Event on Sensorimotor Gating in Adult Rats. Schizophrenia Research, 30, 251-260.
[64] Aasen, I., Kolli, L. and Kumari, V. (2005) Sex Effects in Prepulse Inhibition and Facilitation of the Acoustic Startle Response: Implications for Pharmacological and Treatment Studies. Journal of Psychopharmacology, 19, 39-45.
[65] Plappert, C.F., Rodenbücher, A.M. and Pilz, P.K.D. (2005) Effects of Sex and Estrous Cycle on Modulation of the Acoustic Startle Response in Mice. Physiology & Behavior, 84, 585-594.
[66] Alemán, C.L., Noa, M. Más, R., Rodeiro, I., Menéndez, R., et al. (2000) Reference Data for the Principal Physiological Indicators in Three Species of Laboratory Animals. Laboratory Animals, 34, 379-385.
[67] Ter Horst, G.J., Wichmann, R., Gerrits, M., Westenbroek, C. and Lin, Y. (2009) Sex Differences in Stress Responses: Focus on Ovarian Hormones. Physiology & Behavior, 97, 239-249.
[68] Ordaz, S. and Luna, B. (2012) Sex Differences in Physiological Reactivity to Acute Psychosocial Stress in Adolescence. Psychoneuroendocrinology, 37, 1135-1157.
[69] Bourke, C.H., Harrell, C.S. and Neigh, G.N. (2012) Stress-Induced Sex Differences: Adaptations Mediated by the Glucocorticoid Receptor. Hormones and Behavior, 62, 210-218.
[70] Burghardt, N.S., Sullivan, G.M., McEwen, B.S., Gorman, J.M. and LeDoux, J.E. (2004) The Selective Serotonin Reuptake Inhibitor Citalopram Increases Fear after Acute Treatment but Reduces Fear with Chronic Treatment: A Comparison with Tianeptine. Biological Psychiatry, 55, 1171-1178.
[71] Rossi, D.V., Burke, T.F., McCasland, M. and Hensler, J.G. (2008) Serotonin-1A Receptor Function in the Dorsal Raphe Nucleus Following Chronic Administration of the Selective Serotonin Reuptake Inhibitor Sertraline. Journal of Neurochemistry, 105, 1091-1099.
[72] Goel, N., Innala, L. and Viau, V. (2014) Sex differences in serotonin (5-HT) 1A Receptor Regulation of HPA Axis and Dorsal Raphe Responses to Acute Restraint. Psychoneuroendocrinology, 40, 232-241.
[73] Duchesne, A., Dufresne, M.M. and Sullivan, R.M. (2009) Sex Differences in Corticolimbic Dopamine and Serotonin Systems in the Rat and the Effect of Postnatal Handling. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33, 251-261.
[74] Millan, M.J. (2003) The Neurobiology and Control of Anxious States. Progress in Neurobiology, 70, 83-244.
[75] Sánchez, O., Arnau, A., Pareja, M., Poch, E., Ramírez, I. and Soley, M. (2002) Acute Stress-Induced Tissue Injury in Mice: Differences between Emotional and Social Stress. Cell Stress and Chaperones, 7, 36-46.<0036:ASITII>2.0.CO;2
[76] Dhabhar, F.S. (2007) Enhancing versus Suppressive Effects of Stress on Immune function: Implications for Immunoprotection and Immunopathology. NeuroImmune Biology, 7, 207-224.
[77] Patterson, S.M., Krantz, D.S., Gottdiener, J.S., Hecht, G., Vargot, S. and Goldstein, D.S. (1995) Prothrombotic Effects of Environmental Stress: Changes in Platelet Function, Hematocrit, and Total Plasma Protein. Psychosomatic Medicine, 57, 592-599.
[78] Mischler, K., Fischer, J.E., Zgraggen, L., Kudielka, B.M., Preckel, D. and von Kanel, R. (2005) The Effect of Repeated Acute Mental Stress on Habituation and Recovery Responses in Hemoconcentration and Blood Cells in Healthy Men. Life Sciences, 77, 1166-1179.
[79] von Kanel, R., Preckel, D., Zgraggen, L., Mischler, K., Kudielka, B.M., Haeberli, A., et al. (2004) The Effect of Natural Habituation on Coagulation Responses to Acute Mental Stress and Recovery in Men. Thrombosis and Haemostasis, 92, 1327-1335.
[80] Robbins, T.W. (2005) Chemistry of the Mind: Neurochemical Modulation of Prefrontal Cortical Function. Journal of Comparative Neurology, 493, 140-146.
[81] Arakawa, H., Kodama, H., Matsuoka, N. and Yamaguchi, I. (1997) Stress Increases Plasma Enzyme Activity in Rats: Differential Effects of Adrenergic and Cholinergic Blockades. Journal of Pharmacology and Experimental Therapeutics, 280, 1296-1303.
[82] Chen, S., Xuan, J., Couch, L., Iyer, A., Wu, Y., Li, Q.-Z., et al. (2014) Sertraline Induces Endoplasmic Reticulum Stress in Hepatic Cells. Toxicology, 322, 78-88.
[83] Larrey, D. and Ripault, M.-P. (2013) Chapter 25: Hepatotoxicity of Psychotropic Drugs and Drugs of Abuse. Drug-Induced Liver Disease. 3rd Edition, Academic Press, Boston, 443-462.
[84] Glassman, A.H., O’Connor, C.M., Califf, R.M., Swedberg, K., Schwartz, P., Bigger, J.T., et al. (2002) Sertraline Treatment of Major Depression in Patients with Acute MI or Unstable Angina. JAMA, 288, 701-709.
[85] Haskell, S.E., Peotta, V.A., Reinking, B.E., Hermann, G.M. and Roghair, R.D. (2013) Impact of Neonatal Sertraline Exposure on the Post-Myocardial Infarction Outcomes of Adult Male Mice. Journal of Cardiovascular Pharmacology, 62, 479-484.
[86] Steplewski, Z. and Vogel, W.H. (1986) Total Leukocytes, T Cell Subpopulation and Natural Killer (NK) Cell Activity in Rats Exposed to Restraint Stress. Life Sciences, 38, 2419-2427.
[87] Dhabhar, F.S. (2014) Effects of Stress on Immune Function: The Good, the Bad, and the Beautiful. Immunologic Research, 58, 193-210.
[88] Jones, B.J. and Blackburn, T.P. (2002) The Medical Benefit of 5-HT Research. Pharmacology Biochemistry and Behavior, 71, 555-568.
[89] Zanoveli, J.M., Nogueira, R.L. and Zangrossi, H. (2007) Enhanced Reactivity of 5-HT1A Receptors in the Rat Dorsal Periaqueductal Gray Matter after Chronic Treatment with Fluoxetine and Sertraline: Evidence from the Elevated T-Maze. Neuropharmacology, 52, 1188-1195.
[90] Shelton, R.C. (1994) The Role of Sertraline in the Management of Depression. Clinical Therapeutics, 16, 768-782; Discussion 767.
[91] Kim, S.W., Park, S.Y. and Hwang, O. (2002) Up-Regulation of Tryptophan Hydroxylase Expression and Serotonin Synthesis by Sertraline. Molecular Pharmacology, 61, 778-785.

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