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7 - Wistar–Zagreb 5HT rats: a rodent model with constitutional upregulation/downregulation of serotonin transporter

Published online by Cambridge University Press:  06 July 2010

By
Lipa Cicin-Sain  and
Branimir Jernej
Edited by
Allan V. Kalueff  and
Justin L. LaPorte
Allan V. Kalueff
Affiliation:
Georgetown University Medical Center
Justin L. LaPorte
Affiliation:
National Institute of Mental Health
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Summary

ABSTRACT

By selective breeding for the extreme values of platelet serotonin level (PSL), two sublines of rats with constitutional hyperserotonemia/hyposerotonemia were developed. The velocity of platelet serotonin uptake (PSU), the main determinant of PSL, was used as a further, more specific selection criterion. Directed breeding for its extremes resulted in two sublines of rats with constitutional upregulation/downregulation of platelet 5HT transporter activity, and showed consequent alterations of entire 5HT homeostasis. These sublines, termed Wistar–Zagreb 5HT (WZ-5HT) rats, constitute a genetic rodent model described in this chapter. Besides changes in peripheral 5HT homeostasis, high-5HT and low-5HT sublines of WZ-5HT rats also demonstrate changes in central serotonergic mechanisms. Under physiological conditions, neurochemical differences in the 5HT system between sublines were almost undetectable, but they became evident upon specific pharmacologic challenge as shown by brain microdialysis study. Differential behavioral phenotypes of 5HT sublines in response to various environmental challenges provide further evidence for differences in their brain functioning. Thus, high-5HT rats exhibit enhanced anxiety-like behaviors while depressive-like behavior and higher alcohol intake co-occur in low-5HT rats. Observed functional and behavioral differences between sublines of WZ-5HT rats strongly indicate that brain serotonergic activity was increased in rats from the high-5HT subline as compared to low-5HT rats. The WZ-5HT rat model may represent an integrative model for serotonin and serotonin transporter research, incorporating changes at the genomic/genetic and phenotypic (neurodevelopmental, structural, biochemical, behavioral, etc.) levels, and encompassing both central and peripheral 5HT functioning.

Type
Chapter
Information
Experimental Models in Serotonin Transporter Research , pp. 214 - 243
Publisher: Cambridge University Press
Print publication year: 2010

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References

Lesch, K P, Mossner, R (2006). Inactivation of 5HT transport in mice: modelling altered 5HT homeostasis implicated in emotional dysfunction, affective disorders and somatic syndromes. Handb Exp Pharmacol 175: 417–56.CrossRefGoogle Scholar
Murphy, D L, Lesch, K P (2008). Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9: 85–96.CrossRefGoogle ScholarPubMed
Fox, M A, Andrews, A M, Wendland, J R, Lesch, K P, Holmes, A, Murphy, D L (2007a). A pharmacological analysis of mice with a targeted disruption of the serotonin transporter. Psychopharmacology 195: 147–66.CrossRefGoogle ScholarPubMed
Berger, M, Tecott, L H (2006). Serotonin system gene knockouts. In Roth, B L, editor. The serotonin receptors: from molecular pharmacology to human therapeutics. Totowa: Humana Press, pp. 537–75.CrossRefGoogle Scholar
Bechtholt, A, Lucki, I (2006). Effects of serotonin-related gene deletion on measures of anxiety, depression and neurotransmission. In Roth, B L, editor. The serotonin receptors: from molecular pharmacology to human therapeutics. Totowa: Humana Press, pp. 577–606.CrossRefGoogle Scholar
Shih, J C (2004). Cloning, after cloning, knock-out mice and physiological functions of MAO A and B. Neurotoxicology 25: 21–30.CrossRefGoogle ScholarPubMed
Fernandez, F, Sarre, S, Launay, J M, et al. (2003). Rat strain differences in peripheral and central serotonin transporter protein expression and function. Eur J Neurosci 17: 494–506.CrossRefGoogle ScholarPubMed
Calcagno, E, Cannetta, A, Guzzetti, S, Cervo, L, Ivernizzi, R W (2007). Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity. J Neurochem 103: 1111–20.CrossRefGoogle ScholarPubMed
Staay, F J (2006). Animal models of behavioural dysfunctions: basic concepts and classifications, and an evaluation strategy. Brain Res Rev 52: 131–59.CrossRefGoogle ScholarPubMed
Singewald, N (2007). Altered brain activity processing in high-anxiety rodents revealed by challenge paradigms in functional mapping. Neurosci Biobehav Rev 31: 18–40.CrossRefGoogle ScholarPubMed
Nestler, E J, Gould, E, Manji, H, et al. (2002). Preclinical models: status of basic research in depression. Biol Psychiatry 52: 503–28.CrossRefGoogle ScholarPubMed
Crabbe, J C (2002). Alcohol and genetics: new models. Am J Med Genet 114: 969–74.CrossRefGoogle ScholarPubMed
Pletscher, A (1968). Metabolism, transfer and storage of 5HT in blood platelets. Br J Pharmacol 32: 1–16.Google Scholar
Stahl, S M, Meltzer, H Y (1978). A kinetic and pharmacologic analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: comparison with central serotonergic neurons. J Pharmacol Exp Ther 205: 118–32.Google ScholarPubMed
Chen, K, Wu, H F, Shih, J C (1993). The deduced amino acid sequences of human platelet and frontal cortex monoamine oxidase B are identical. J Neurochem 61: 187–90.CrossRefGoogle ScholarPubMed
Cook, E H, Fletcher, K E, Wainwright, M, Marks, N, Yan, S Y, Leventhal, B L (1994). Primary structure of the human platelet serotonin 5HT2A receptor: identity with the frontal cortex serotonin 5HT2A receptor. J Neurochem 63: 465–9.CrossRefGoogle Scholar
Lesch, K P, Wolozin, B L, Murphy, D L, Riederer, P (1993). Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem 60: 2319–21.CrossRefGoogle ScholarPubMed
Pletscher, A (1988). Platelets as models: use and limitations. Experientia 44: 152–5.CrossRefGoogle ScholarPubMed
Hrdina, P D (1994). Platelet serotonergic markers in psychiatric disorders: use, abuse and limitations. J Psychiatry Neurosci 19: 87–90.Google ScholarPubMed
Jernej, B (1995). Platelet versus neuron: a glimpse from serotonergic perspective. Period Biol 97: 183–90.Google Scholar
Camacho, A, Dimsdale, J E (2000). Platelets and psychiatry: lessons learned from old and new studies. Psychosom Med 62: 326–36.CrossRefGoogle ScholarPubMed
Jernej, B, Cicin-Sain, L, Iskric, S (1988). A simple and reliable method for monitoring platelet serotonin levels in rats. Life Sci 43: 1663–70.CrossRefGoogle ScholarPubMed
Jernej, B, Froebe, A, Hranilovic, D, Cicin-Sain, L (1999a). Platelet serotonin transporter: ex vivo monitoring of kinetic parameters in the individual rat. Neurosci Res Comm 24: 163–72.3.0.CO;2-W>CrossRefGoogle Scholar
Jernej, B, Cicin-Sain, L, Kveder, S (1989). Physiological characteristics of platelet serotonin in rats. Life Sci 45: 485–92.CrossRefGoogle ScholarPubMed
Cicin-Sain, L, Jernej, B, Magnus, V (1989). Platelet serotonin levels and gonadal hormones in rats. Life Sci 45: 1885–92.CrossRefGoogle ScholarPubMed
Cicin-Sain, L, Froebe, A, Jernej, B (1998). Physiological characteristics of serotonin transporter on rat platelets. Comp Biochem Phys A 120: 723–9.CrossRefGoogle ScholarPubMed
Jernej, B, Cicin-Sain, L (1990). Platelet serotonin level in rats is under genetic control. Psychiat Res 32: 167–74.CrossRefGoogle ScholarPubMed
Cicin-Sain, L, Perovic, S, Iskric, S, Jernej, B (1995). Development of sublines of Wistar-derived rats with high or low platelet serotonin level. Period Biol 97: 211–16.Google Scholar
Cicin-Sain, L, Froebe, A, Bordukalo-Niksic, T, Jernej, B (2005). Serotonin transporter kinetics in rats selected for extreme values of platelet serotonin level. Life Sci 77: 452–61.CrossRefGoogle ScholarPubMed
Hranilovic, D, Herak-Kramberger, C, Cicin-Sain, L, Sabolic, I, Jernej, B (2001). Serotonin transporter in rat platelets: level of protein expression underlies inherited differences in uptake kinetics. Life Sci 69: 59–65.CrossRefGoogle ScholarPubMed
Bordukalo-Niksic, T, Cicin-Sain, L, Jernej, B (2004). Expression of brain and platelet serotonin transporters in sublines of rats with constitutionally altered serotonin homeostasis. Neurosci Lett 369: 44–9.CrossRefGoogle ScholarPubMed
Jernej, B, Hranilovic, D, Cicin-Sain, L (1999b). Serotonin transporter on rat platelets: level of mRNA underlie inherited differences in uptake kinetics. Neurochem Int 33: 519–23.CrossRefGoogle Scholar
Anderson, G M, Stevenson, J M, Cohen, D J (1987). Steady-state model for plasma-free and platelet serotonin in man. Life Sci 41: 1777–85.CrossRefGoogle ScholarPubMed
Fozard, J R (1989). The peripheral actions of 5-hydroxytryptamine. New York: Oxford University Press.Google Scholar
Dube, F, Amireault, P (2007). Local serotonergic signaling in mammalian follicles, oocytes and early embrios. Life Sci 81: 1627–37.CrossRefGoogle Scholar
Hull, E M, Muschamp, J W, Sato, S (2004). Dopamine and serotonin: influences on male sexual behavior. Physiol Behav 83: 291–307.CrossRefGoogle ScholarPubMed
Gershon, M D, Tack, J (2007). The serotonin signalling system: from basic understanding to drug development for functional GI disorders. Gastroententerology 132: 397–414.CrossRefGoogle Scholar
Watts, S W (2005). 5-HT in systemic hypertension: foe, friend or fantasy?Clin Sci (Lond.) 108: 399–412.CrossRefGoogle ScholarPubMed
Blakely, R D (2001). Physiological genomics of antidepressant targets: keeping periphery in mind. J Neurosci 21: 8319–23.CrossRefGoogle ScholarPubMed
Murphy, D L, Lerner, A, Rudnick, G, Lesch, K P (2004). Serotonin transporter: gene, genetic disorders and pharmacogenetics. Mol Interv 4: 109–23.CrossRefGoogle ScholarPubMed
Cicin-Sain, L, Oreskovic, D, Perovic, S, Jernej, B, Iskric, S (1990). Determination of serotonin in peripheral rat tissues by ion-exchange chromatography-fluorometry. Validation by high performance liquid chromatography with electrochemical detection. Biogen Amines 7: 641–50.Google Scholar
Ortiz, J, Artigas, F (1992). Effects of monoamine uptake inhibitors on extracellular and platelet 5-hydroxytryptamine in rat blood: different effects of clomipramine and fluoxetine. Br J Pharmacol 105: 941–6.CrossRefGoogle ScholarPubMed
Mekontso-Dessap, A, Brouri, F, Pascal, O, et al. (2006). Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice. Circulation 113: 81–9.CrossRefGoogle ScholarPubMed
Guignabert, C, Izikki, M, Tu, L I, et al. (2006). Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res 98: 1323–30.CrossRefGoogle ScholarPubMed
Janusonis, S, Anderson, G M, Shifrovich, I, Rakic, P (2006). Ontogeny of brain and blood serotonin levels in 5-HT1A receptor knockout mice: potential relevance to the neurobiology of autism. J Neurochem 99: 1019–31.CrossRefGoogle ScholarPubMed
Cicin-Sain, L, Froebe, A, Jernej, B (1996). The effect of antidepressants on platelet serotonin level and serotonin uptake in rats genetically selected for these traits. Eur Neuropsychopharm 6 (Suppl. 4): 76–7.CrossRefGoogle Scholar
Binder, E B, Holsboer, F (2006). Pharmacogenomics and antidepressant drugs. Ann Med 38: 82–94.CrossRefGoogle ScholarPubMed
Serretti, A, Benedetti, F, Zanardi, R, Smeraldi, E (2005). The influence of serotonin transporter promoter polymorphism (SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments. Prog Neuropsychopharmacol Biol Psychiatry 29: 1074–84.CrossRefGoogle ScholarPubMed
Lesch, K P, Gutknecht, L (2005). Pharmacogenetics of the serotonin transporter. Prog Neuropsychopharmacol Biol Psychiatry 29: 1062–73.CrossRefGoogle ScholarPubMed
Lesch, K P, Mossner, R (1998). Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental and neurodegenerative disorders. Biol Psychiatry 44: 179–92.CrossRefGoogle Scholar
Jernej, B, Cicin-Sain, L, Banovic, M (1994). Platelet aggregation in rats genetically selected for high or low platelet serotonin levels. Can J Physiol Pharmacol 72 (Suppl. 1): 10.Google Scholar
Clerck, F, Chaffoy de Courcelles, D (1990). Serotonergic amplification in platelet function: mechanisms and in vivo relevance. In Progress in pharmacology and clinical pharmacology 7/4. Stuttgart: Gustav Fischer Verlag, pp. 51–9.Google Scholar
Froebe, A, Cicin-Sain, L, Jernej, B (1997). Intracellular calcium in platelets of rats with genetically altered serotonin system. Period Biol 99 (Suppl. 1): 85.Google Scholar
Froebe, A (2006). Serotonin-2A receptor and its signaling: studies in rats with altered serotonergic homeostasis. PhD Thesis, University of Zagreb, pp. 1–83.Google Scholar
Vanhoutte, P M (1985). Serotonin and the cardiovascular system. New York: Raven Press.Google Scholar
Vorchheimer, D A, Becker, R (2006). Platelets in atherothrombosis. Mayo Clin Proc 81: 59–68.CrossRefGoogle ScholarPubMed
Hegedis, K (2001). Serotonin transporter: kinetic studies in rat cerebral cortex. MSc Thesis, University of Zagreb, pp. 1–61.Google Scholar
Perez, X A, Bianco, L E, Andrews, A M (2006). Filtration disrupts synaptosomes during radiochemical analysis of serotonin uptake: comparison with chronoamperometry in SERT knockout mice. J Neurosci Methods 154: 245–55.CrossRefGoogle ScholarPubMed
Bengel, D, Murphy, D L, Andrews, A, et al. (1998). Altered brain serotonin homeostasis and locomotor insensitivity to 3,4-methylendioxymethamphetamine (“ecstasy”) in serotonin transporter-deficient mice. Mol Pharmacol 53: 649–55.CrossRefGoogle Scholar
Perez, X A, Andrews, A M (2005). Chronoamperometry to determine differential reductions in uptake in brain synaptosomes from serotonin transporter knockout mice. Anal Chem 77: 818–26.CrossRefGoogle ScholarPubMed
Homberg, J R, Olivier, J D A, Smits, B M G, et al. (2007). Characterization of the serotonin transporter knockout rat: a selective change in the functioning of the serotonergic system. Neuroscience 146: 1662–76.CrossRefGoogle ScholarPubMed
Romero, L, Jernej, B, Bel, N, Cicin-Sain, L, Cortes, R, Artigas, F (1998). Basal and stimulated extracellular serotonin concentration in the brain of rats with altered serotonin uptake. Synapse 28: 313–21.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Jayanthi, L D, Ramamoorthy, S (2005). Regulation of monoamine transporters: influence of psychostimulants and therapeutic antidepressants. Am Ass Pharmaceut Sci J 7: E728–38.Google ScholarPubMed
Zahniser, N R, Doolen, S (2001). Chronic and acute regulation of Na+/Cl–-dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems. Pharmacol Ther 92: 21–55.CrossRefGoogle Scholar
Bokulic, Z, Cicin-Sain, L, Jernej, B (2003). Wistar–Zagreb 5HT rats: study of serotonergic activity in brain regions. Neurol Croat 52 (Suppl.): 91.Google Scholar
Kim, D K, Tolliver, T J, Huang, S J, et al. (2005). Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter. Neuropharmacology 49: 798–810.CrossRefGoogle ScholarPubMed
Zhao, S, Edwards, J, Carroll, J, et al. (2006). Insertion mutation at the C-terminus of the serotonin transporter disrupts brain serotonin function and emotion-related behaviors in mice. Neuroscience 140: 321–34.CrossRefGoogle ScholarPubMed
Stefulj, J (2005). Tryptophan hydroxylase: polymorphism and expression of the gene in altered serotonergic homeostasis. PhD Thesis, University of Zagreb, pp. 1–76.Google Scholar
Montanez, S, Owens, W A, Gould, G G, Murphy, D L, Daws, L C (2003). Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice. J Neurochem 86: 210–9.CrossRefGoogle ScholarPubMed
Mathews, T A, Fedele, D E, Coppelli, F M, Avila, A M, Murphy, D L, Andrews, A M (2004). Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression. J Neurosci Methods 140: 169–81.CrossRefGoogle Scholar
Fabre, V, Beaufour, C, Evrard, A, et al. (2000). Altered expression and function of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5HT transporter. Eur J Neurosci 12: 2299–310.CrossRefGoogle Scholar
Jennings, K A, Loder, M K, Sheward, W J, et al. (2006). Increased expression of the 5HT transporter confers a low-anxiety phenotype linked to decreased 5HT transmission. J Neurosci 26: 8955–64.CrossRefGoogle Scholar
Wagstaff, A J, Ormrod, D, Spencer, C M (2001). Tianeptine: a review of its use in depressive disorders. CNS Drugs 15: 231–59.CrossRefGoogle ScholarPubMed
Hariri, A R, Holmes, A (2006). Genetics of emotional regulation: the role of the serotonin transporter in neuronal function. Trends Cogn Sci 10: 182–91.CrossRefGoogle Scholar
Li, Q, Wichems, C H, Ma, L, Kar, L D, Garcia, F, Murphy, D L (2003). Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice. J Neurochem 84: 1256–65.CrossRefGoogle ScholarPubMed
Rioux, A, Fabre, V, Lesch, K P, et al. (1999). Adaptive changes of serotonin 5-HT2A receptors in mice lacking the serotonin transporter. Neurosci Lett 262: 113–6.CrossRefGoogle ScholarPubMed
Bordukalo-Niksic, T, Mokrovic, G, Jernej, B, Cicin-Sain, L (2007). Expression of 5HT-1A and 5HT-1B receptor genes in brains of Wistar–Zagreb 5HT rats. Coll Antropol 31: 37–41.Google Scholar
Bordukalo-Niksic, T (2003). Gene expression of 5HT-synaptic elements in brain of rats with altered serotonin homeostasis. MSc Thesis, University of Zagreb, pp. 1–73.Google Scholar
Froebe, A, Cicin-Sain, L, Bordukalo-Niksic, T, Jernej, B (2007). Serotonin-2A receptors and its signal transduction in brains and platelets of Wistar–Zagreb 5HT rats. Neurol Croat 56 (Suppl. 2): 7.Google Scholar
Isbister, G K, Buckley, N A (2005). The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol 28: 205–14.CrossRefGoogle ScholarPubMed
Kalueff, A V, LaPorte, J, Murphy, D L (2007b). Perspectives on genetic animal models of serotonin toxicity. Neurochem Int 52: 649–58.CrossRefGoogle ScholarPubMed
Fox, M A, Jensen, C L, Gallagher, P S, Murphy, D L (2007b). Receptor mediation of exaggerated response to serotonin-enhancing drugs in serotonin transporter (SERT)-deficient mice. Neuropharmacology 53: 643–56.CrossRefGoogle ScholarPubMed
Oekelen, D, Megens, A, Meert, T, Luyten, W H, Leysen, J E (2002). Role of 5HT2 receptors in the tryptamine-induced 5HT syndrome in rats. Behav Pharmacol 13: 313–8.CrossRefGoogle Scholar
Nisijima, K, Yoshino, T, Yui, K, Katoh, S (2001). Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Res 890: 23–31.CrossRefGoogle Scholar
Briley, M, Chopin, P (1991). Serotonin in anxiety: evidence from animal models. In Sandler, M, Coppen, A, Harnett, S, editors. 5-Hydroxytryptamine in psychiatry: a spectrum of ideas. New York: Oxford University Press, pp. 177–97.CrossRefGoogle Scholar
Lesch, K P, Zeng Y, Reif A, Gutknecht, L (2003). Anxiety-related traits in mice with modified genes of the serotonergic pathway. Eur J Phamacol 480: 185–204.CrossRefGoogle ScholarPubMed
Holmes, A, Li, Q, Murphy, D L, Gold, E, Crawley, J N (2003). Abnormal anxiety related behavior in serotonin transporter null mutant mice: the influence of genetic background. Genes Brain Behav 2: 365–80.CrossRefGoogle ScholarPubMed
Hranilovic, D, Cicin-Sain, L, Bordukalo-Niksic, T, Jernej, B (2005). Rats with constitutionally upregulated/downregulated platelet 5HT transporter: differences in anxiety-related behavior. Behav Brain Res 165: 271–7.CrossRefGoogle ScholarPubMed
Quevedo, G, Moscoso, O, Prado-Moreno, A, Cicin-Sain, L, Jernej, B, Delgado-Garcia, J M (2002). Behavioral and molecular studies in rats over-expressing and under-expressing serotonin transporter. COST B10: Brain Damage Repair, 11th Committee Meeting, Dublin, Abstract book, p. 15.Google Scholar
Ansorge, M S, Zhou, M, Lira, A, Hen, R, Gingrich, J A (2004). Early-life blockade of the 5HT transporter alters emotional behavior in adult mice. Science 306: 879–81.CrossRefGoogle ScholarPubMed
Kalueff, A V, Fox, M A, Gallagher, P S, Murphy, D L (2007a). Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice. Gen Brain Behav 6: 389–400.CrossRefGoogle ScholarPubMed
Mann, J (1999). Role of serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology 21: 99S–105S.CrossRefGoogle ScholarPubMed
Ordway, G A, Klimek, V, Mann, J J (2002). Neurocircuitry of mood disorders. In Davis, K L, Charney, D, Coyle, J T, Nemeroff, C, editors. Neuropsychopharmacology – the fifth generation of progress. Philadelphia: Lippincott, Williams and Wilkins, pp. 1051–64.Google Scholar
Blier, P, Montigny, C (1994). Current advances and trends in the treatment of depression. Trends Pharmacol Sci 15: 220–6.CrossRefGoogle ScholarPubMed
Ressler, K J, Nemeroff, C B (2000). Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety 12: 2–19.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Kalueff, A V, Tuohimaa, P (2004). Experimental modelling of anxiety and depression. Acta Neurobiol Exp 64: 439–48.Google Scholar
Cryan, J F, Markou, A, Lucki, I (2002). Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23: 238–45.CrossRefGoogle ScholarPubMed
Detke, M J, Rickels, M, Lucki, I (1995). Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 121: 66–72.CrossRefGoogle ScholarPubMed
Reneric, J P, Bouvard, M, Stinus, L (2002). In the rat forced swimming test, chronic but not subacute administration of dual 5-HT/NA antidepressant treatments, may produce greater effects than selective drugs. Behav Brain Res 136: 521–32.CrossRefGoogle Scholar
Lira, A, Zhou, M, Castanon, N, et al. (2003). Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter deficient mice. Biol Psychiatry 54: 960–71.CrossRefGoogle ScholarPubMed
Holmes, A, Yang, R J, Murphy, D L, Crawley, J N (2002). Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 27: 914–23.CrossRefGoogle ScholarPubMed
Kalueff, A V, Gallagher, P S, Murphy, D L (2006). Are serotonin transporter knockout mice depressed? Hypoactivity but no anhedonia. Neuroreport 17: 1347–51.CrossRefGoogle ScholarPubMed
Olivier, J D A, Hart, M G C, Swelm, R P L, et al. (2008). A study in male and female 5HT transporter knockout rats: an animal model for anxiety and depression disorders. Neuroscience 152: 573–84.CrossRefGoogle ScholarPubMed
LeMarquand, D, Phil, R O, Benkelfat, C (1994b). Serotonin and alcohol intake, abuse and dependence: findings of animal studies. Biol Psychiatry 36: 395–421.CrossRefGoogle ScholarPubMed
LeMarquand, D, Phil, R O, Benkelfat, C (1994a). Serotonin and alcohol intake, abuse and dependence: clinical evidence. Biol Psychiatry 36: 326–37.CrossRefGoogle ScholarPubMed
Lesch, K P (2005). Alcohol dependence and gene × environment interaction in emotion regulation: is serotonin the link?Eur J Pharmacol 526: 113–24.CrossRefGoogle ScholarPubMed
Cicin-Sain, L, Bordukalo-Niksic, T, Jernej, B (2004). Wistar–Zagreb 5HT rats: a new animal model of alcoholism. Alcoholism 40 (Suppl. 3): 92–3.Google Scholar
McBride, W J, Li, T K (1998). Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol 12: 339–69.CrossRefGoogle ScholarPubMed
Mokrovic, G, Cicin-Sain, L (2006). Chronic ethanol intake and brain monoamine oxidase A and B in rats with constitutionally altered serotonin homeostasis. 5th Forum of European Neuroscience, Vienna, book of abstracts, A165.19.
Kelai, S, Aissi, F, Lesch, K P, Cohen-Salmon, C, Hamon, M, Lanfumey, L (2003). Alcohol intake after serotonin transporter inactivation in mice. Alcohol Alcohol 38: 386–9.CrossRefGoogle ScholarPubMed
Boyce-Rustay, J M, Wiedholz, L M, Millstein, R A, et al. (2006). Ethanol-related behaviors in serotonin transporter knockout mice. Alcohol Clin Exp Res 30: 1957–65.CrossRefGoogle ScholarPubMed
Gabrilovac, J, Cicin-Sain, L, Osmak, M, Jernej, B (1992). Alteration of NK- and ADCC-activities in rats genetically selected for low or high platelet serotonin level. J Neuroimmunol 37: 213–22.CrossRefGoogle ScholarPubMed
Poljak-Blazi, M, Jernej, B, Cicin-Sain, L, Boranic, M (1990). Immunological response of rats selected for high or low platelet serotonin content. Period Biol 92: 189–90.Google Scholar
Djurkovic, M, Tvrdeic, A, Cicin-Sain, L, Jernej, B, Birus, I (2004). Pain sensitivity in Wistar and Wistar–Zagreb 5HT rats: the effect of habituation to experimental conditions. Fourth Croatian Congress of Pharmacology, Split, book of abstracts, p. 78.

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