Top

Published in:

01-06-2014 | Original Paper

Changes in behavior and ultrasonic vocalizations during antidepressant treatment in the maternally separated Wistar-Kyoto rat model of depression

Authors: P. J. van Zyl, J. J. Dimatelis, V. A. Russell

Published in: Metabolic Brain Disease | Issue 2/2014

Abstract

Genetic predisposition and stress are major factors in depression. The objective of this study was to establish a robust animal model of depression by selecting the appropriate substrain of the Wistar-Kyoto (WKY) rat, and subjecting these rats to the stress of maternal separation during the early stages of development. The initial experiment identified WKY/NCrl as the appropriate substrain of WKY to use for the study. In the second part of the study, depression-like behavior and ultrasonic vocalizations (USVs) were recorded in WKY/NCrl and maternally separated WKY/NCrl rats during the course of reversal of depression-like behavior. Wistar rats served as the reference strain. In adulthood, non-separated WKY/NCrl, maternally separated WKY/NCrl and Wistar rats were injected intraperitoneally with either saline or desipramine (15 mg/kg/day) for 15 days and their behavior recorded. Desipramine decreased immobility and increased active swimming and struggling behavior of WKY/NCrl in the FST and also decreased their USVs in response to removal of cage mates. The USVs in this study appeared to signal an attempt to re-establish social contact with cage mates and provided a measure of social dependence. Maternally separated WKY/NCrl rats displayed more anxiety than normally reared WKY/NCrl rats and responded to the anxiolytic effects of desipramine. The present findings support the use of WKY/NCrl as an animal model of depression. Maternal separation increased the anxiety-like behavior of the WKY/NCrl, thus providing a robust model to study depression- and anxiety-related behavior.

Armario A, Gavalda A, Marti O (1988) Forced swimming test in rats: effects of desipramine administration and the period of exposure to the test on struggling behavior, swimming, immobility and defecation rate. Eur J Pharmacol 158:207–212PubMedCrossRef

Berton O, Ramos A, Chaouloff F, Mormède P (1997) Behavioral reactivity to social and nonsocial stimulations: a multivariate analysis of six inbred rat strains. Behav Genet 27:155–166PubMedCrossRef

Blanchard RJ, Blanchard DC, Agullana R, Weiss SM (1991) Twenty-two kHz alarm cries to presentation of a predator, by laboratory rats living in visible burrow systems. Physiol Behav 50:967–972PubMedCrossRef

Brudzynski SM, Pniak A (2002) Social contacts and production of 50-kHz short ultrasonic calls in adult rats. J Comp Psychol 116:73–82PubMedCrossRef

Burgdorf J, Panksepp J (2006) The neurobiology of positive emotions. Neurosci Biobehav Rev 30:173–187PubMedCrossRef

Burgdorf J, Knutson B, Panksepp J (2000) Anticipation of rewarding electrical brain stimulation evokes ultrasonic vocalization in rats. Behav Neurosci 114:320–327PubMedCrossRef

Burgdorf J, Kroes RA, Moskal JR, Brudzynski SM, Pfaus JG, Panksepp J (2008) Ultrasonic vocalizations of rats (Rattus norvegicus) during mating, play, and aggression: behavioral concomitants, relationship to reward, and self-administration of playback. J Comp Psychol 122:357–367PubMedCrossRef

Burgdorf J, Panksepp J, Moskal JR (2011) Frequency-modulated 50 kHz ultrasonic vocalizations: a tool for uncovering the molecular substrates of positive affect. Neurosci Biobehav Rev 35:1831–1836PubMedCrossRef

Burman OHP, Ilyat A, Jones G, Mendl M (2007) Ultrasonic vocalizations as indicators of welfare for laboratory rats (Rattus norvegicus). Appl Anim Behav Sci 104:116–129CrossRef

Costa R, Tamascia ML, Nogueira MD, Casarini DE, Marcondes FK (2012) Handling of adolescent rats improves learning and memory and decreases anxiety. J Am Assoc Lab Anim Sci JAALAS 51:548–553

Daniels WMU, Pietersen CY, Carstens ME, Stein DJ (2004) Maternal separation in rats leads to anxiety-like behavior and a blunted ACTH response and altered neurotransmitter levels in response to a subsequent stressor. Metab Brain Dis 19:3–14PubMedCrossRef

Detke MJ, Lucki I (1995) Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: the effects of water depth. Behav Brain Res 73:43–46CrossRef

Deupree JD, Reed AL, Bylund DB (2007) Differential effects of the tricyclic antidepressant desipramine on the density of adrenergic receptors in juvenile and adult rats. J Pharmacol Exp Ther 321:770–776PubMedCentralPubMedCrossRef

Dimatelis JJ, Stein DJ, Russell VA (2012) Behavioral changes after maternal separation are reversed by chronic constant light treatment. Brain Res 1480:61–71PubMedCrossRef

Farrell WJ, Alberts JR (2002) Maternal responsiveness to infant Norway rat (Rattus norvegicus) ultrasonic vocalizations during the maternal behavior cycle and after steroid and experiential induction regimens. J Comp Psychol 116:286–296PubMedCrossRef

Grant MM, Weiss JM (2001) Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity. Biol Psychiatry 49:117–129PubMedCrossRef

Jeannotte AM, McCarthy JG, Redei EE, Sidhu A (2009) Desipramine modulation of alpha- gamma-synuclein, and the norepinephrine transporter in an animal model of depression. Neuropsychopharmacology 34:987–998PubMedCrossRef

Kalinichev M, Easterling KW, Plotsky PM, Holtzman SG (2002) Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats. Pharmacol Biochem Behav 73:131–140PubMedCrossRef

Keers R, Uher R (2012) Gene-environment interaction in major depression and antidepressant treatment response. Curr Psychiatr Rep 14:129–137CrossRef

Kendler KS, Kessler RC, Waiters EE, MacLean C, Neale MC, Heath AC, Eaves LJ (1995) Stressful life events, genetic liability, and onset of an episode of major depression in women. Am J Psychiatr 152:833–842PubMed

Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Kim YH, Yoon JS (2007) Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biol Psychiatry 62:423–428PubMedCrossRef

Knutson B, Burgdorf J, Panksepp J (1998) Anticipation of play elicits high-frequency ultrasonic vocalizations in young rats. J Comp Psychol 112:65–73PubMedCrossRef

Knutson B, Burgdorf J, Panksepp J (2002) Ultrasonic vocalizations as indices of affective states in rats. Psychol Bull 128:961–977PubMedCrossRef

Kulkarni SK, Dandiya PC (1973) Effects of antidepressant agents on open field behaviour in rats. Psychopharmacologia 33:333–338PubMedCrossRef

Kuma H, Miki T, Matsumoto Y, Gu H, Li HP, Kusaka T, Satriotomo I, Okamoto H, Yokoyama T, Bedi S, Onishi S, Suwaki H, Takeuchi Y (2004) Early maternal deprivation induces alterations in brain-derived neurotrophic factor expression in the developing rat hippocampus. Neurosci Lett 372:68–73PubMedCrossRef

Kurtz TW, Montano M, Chan L, Kabra P (1989) Molecular evidence of genetic heterogeneity in Wistar-Kyoto rats: implications for research with the spontaneously hypertensive rats. Hypertension 13:188–192PubMedCrossRef

Lahmame A, Armario A (1996) Differential responsiveness of inbred strains of rats to antidepressants in the forced swimming test: are Wistar Kyoto rats an animal model of subsensitivity to antidepressants? Psychopharmacology 123:191–198PubMedCrossRef

Lahmame A, del Arco C, Pazos A, Yritia M, Armario A (1997) Are Wistar-Kyoto rats a genetic animal model of depression resistant to antidepressants? Eur J Pharmacol 337:115–123PubMedCrossRef

Lee JH, Kim HJ, Kim JG, Ryu V, Kim BT, Kang DW, Jahng JW (2007) Depressive behaviors and decreased expression of serotonin reuptake transporter in rats that experienced neonatal maternal separation. Neurosci Res 58:32–39PubMedCrossRef

Lopez-Rubalcava C, Lucki I (2000) Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology 22:191–199PubMedCrossRef

Lucki I (1997) The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 8:523–532PubMedCrossRef

Lyubomirsky S, King L, Diener E (2005) The benefits of frequent positive affect: does happiness lead to success? Psychol Bull 131:803–855PubMedCrossRef

Malkesman O, Braw Y, Zagoory-Sharon O, Golan O, Lavi-Avnon Y, Schroeder M, Overstreet DH, Yadid G, Weller A (2005) Reward and anxiety in genetic animal models of childhood depression. Behav Brain Res 164:1–10PubMedCrossRef

Mällo T, Matrov D, Herm L, Kõiv K, Eller M, Rinken A, Harro J (2007) Tickling-induced 50-kHz ultrasonic vocalization is individually stable and predicts behaviour in tests of anxiety and depression in rats. Behav Brain Res 184:57–71PubMedCrossRef

Mällo T, Matrov D, Kõiv K, Harro J (2009) Effect of chronic stress on behavior and cerebral oxidative metabolism in rats with high or low positive affect. Neuroscience 164:963–974PubMedCrossRef

Marais L, van Rensburg SJ, van Zyl JM, Stein DJ, Daniels WMU (2008) Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus. Neurosci Res 61:106–112PubMedCrossRef

Miczek KA, Weerts EM, Vivian JA, Barros HM (1995) Aggression, anxiety and vocalizations in animals: GABAA and 5-HT anxiolytics. Psychopharmacology 121:38–56PubMedCrossRef

Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D (2006) The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry 60:1046–1052PubMedCrossRef

Murray CJL, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet 349:1436–1442PubMedCrossRef

Natusch C, Schwarting RKW (2010) Using bedding in a test environment critically affects 50-kHz ultrasonic vocalizations in laboratory rats. Pharmacol Biochem Behav 96:251–259PubMedCrossRef

Nestler EJ, McMahon A, Sabban EL, Tallman JF, Duman RS (1990) Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus. Proc Natl Acad Sci U S A 87:7527–7531CrossRef

Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM (2002) Neurobiology of depression. Neuron 34:13–25PubMedCrossRef

Nosek K, Dennis K, Andrus BM, Ahmadiyeh N, Baum AE, Woods LCS, Redei EE (2008) Context and strain-dependent behavioral response to stress. Behav Brain Funct 4:1–8CrossRef

Okamoto K, Aoki K (1963) Development of a strain of spontaneously hypertensive rats. Jpn Circ J 27:282–293PubMedCrossRef

Paetsch PR, Greenshaw AJ (1993) Effects of chronic antidepressant treatment on beta-adrenoceptor subtype binding in the rat cerebral cortex and cerebellum. Mol Chem Neuropathol 20:21–31PubMedCrossRef

Panksepp J, Burgdorf J (2000) 50-kHz chirping (laughter?) in response to conditioned and unconditioned tickle-induced reward in rats: effects of social housing and genetic variables. Behav Brain Res 115:25–38PubMedCrossRef

Pardon MC, Gould GG, Garcia A, Phillips L, Cook MC, Miller SA, Mason PA, Morilak DA (2002) Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: implications for susceptibility to stress-related neuropsychiatric disorders. Neuroscience 115:229–242PubMedCrossRef

Paré WP (1989) “Behavioral despair” test predicts stress ulcer in WKY rats. Physiol Behav 46:483–487PubMedCrossRef

Paré WP (1992) Learning behavior, escape behavior, and depression in an ulcer susceptible rat strain. Integr Physiol Behav Sci 27:130–141PubMedCrossRef

Paré WP (2000) Investigatory behavior of a novel conspecific by Wistar Kyoto, Wistar and Sprague–Dawley rats. Brain Res Bull 53:759–765PubMedCrossRef

Paré WP, Kluczynski J (1997) Differences in the stress response of Wistar-Kyoto (WKY) rats from different vendors. Physiol Behav 62:643–648PubMedCrossRef

Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732PubMedCrossRef

Portfors CV (2007) Types and functions of ultrasonic vocalizations in laboratory rats and mice. J Am Assoc Lab Anim Sci JAALAS 46:28–34

Racagni G, Brunello N (1984) Transynaptic mechanisms in the action of antidepressant drugs. Trends Pharmacol Sci 5:527–531CrossRef

Racagni G, Mocchetti I, Calderini G, Battistella A, Brunello N (1983) Temporal sequence of changes in central noradrenergic system of rat after prolonged antidepressant treatment: receptor desensitization and neurotransmitter interactions. Neuropharmacology 22:415–424PubMedCrossRef

Rodgers RJ, Johnson NJT (1995) Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety. Pharmacol Biochem Behav 52:297–303PubMedCrossRef

Rosenzweig-Lipson S, Beyer CE, Hughes ZA, Khawaja X, Rajarao SJ, Malberg JE, Rahman Z, Ring RH, Schechter LE (2007) Differentiating antidepressants of the future: efficacy and safety. Pharmacol Ther 113:134–153PubMedCrossRef

Sagvolden T, DasBanerjee T, Zhang-James Y, Middleton FA, Faraone SV (2008) Behavioral and genetic evidence for a novel animal model of attention-deficit/hyperactivity disorder predominantly inattentive subtype. Behav Brain Funct 4:1–11CrossRef

Sagvolden T, Johansen EB, Wøien G, Walaas SI, Storm-Mathisen J, Bergersen LH, Hvalby Ø, Jensen V, Aase H, Russell VA, Killeen PR, DasBanerjee T, Middleton FA, Faraone SV (2009) The spontaneously hypertensive rat model of ADHD—the importance of selecting the appropriate reference strain. Neuropharmacology 57:619–626PubMedCentralPubMedCrossRef

Sánchez C (2003) R-citalopram attenuates anxiolytic effects of escitalopram in a rat ultrasonic vocalisation model. Eur J Pharmacol 464:155–158PubMedCrossRef

Schmitt U, Hiemke C (1998) Strain differences in open-field and elevated plus-maze behavior of rats without and with pretest handling. Pharmacol Biochem Behav 59:807–811PubMedCrossRef

Seyfarth RM, Cheney DL (2003) Meaning and emotion in animal vocalizations. N Y Acad Sci Ann 1000:32–55CrossRef

Solberg LC, Olson SL, Turek FW, Redei E (2001) Altered hormone levels and circadian rhythm of activity in the WKY rat, a putative animal model of depression. Am J Physiol Regul Integr Comp Physiol 281:R786–R794PubMed

Subhash MN, Nagaraja MR, Sharada S, Vinod KY (2003) Cortical alpha-adrenoceptor downregulation by tricyclic antidepressants in the rat brain. Neurochem Int 43:603–609PubMedCrossRef

Takahashi LK, Thomas DA, Barfield RJ (1983) Analysis of ultrasonic vocalizations emitted by residents during aggressive encounters among rats (Rattus norvegicus). J Comp Psychol 97:207–212PubMedCrossRef

Taylor SE, Lerner JS, Sage RM, Lehman BJ, Seeman TE (2004) Early environment, emotions, responses to stress, and health. J Pers 72:1365–1393PubMedCrossRef

Tejani-Butt SM, Paré WP, Yang J (1994) Effect of repeated novel stressors on depressive behavior and brain norepinephrine receptor system in Sprague–Dawley and Wistar Kyoto (WKY) rats. Brain Res 649:27–35PubMedCrossRef

Tejani-Butt S, Kluczynski J, Paré WP (2003) Strain-dependent modification of behavior following antidepressant treatment. Prog Neuro-Psychopharmacol Biol Psychiatry 27:7–14CrossRef

Thomas DA, Takahashi LK, Barfield RJ (1983) Analysis of ultrasonic vocalizations emitted by intruders during aggressive encounters among rats (Rattus norvegicus). J Comp Psychol 97:201–206PubMedCrossRef

Tizabi Y, Bhatti BH, Manaye KF, Das JR, Akinfiresoye L (2012) Antidepressant-like effects of low ketamine dose is associated with increased hippocampal AMPA/NMDA receptor density ratio in female Wistar-Kyoto rats. Neuroscience 213:72–80PubMedCentralPubMedCrossRef

Tornatzky W, Miczek KA (1995) Alcohol, anxiolytics and social stress in rats. Psychopharmacology 121:135–144PubMedCrossRef

Tucker JC, File SE (1986) The effects of tricyclic and ‘atypical’ antidepressants on spontaneous locomotor activity in rodents. Neurosci Biobehav Rev 10:115–121PubMedCrossRef

Vivian JA, Miczek KA (1991) Ultrasounds during morphine withdrawal in rats. Psychopharmacology 104:187–193PubMedCrossRef

Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2:322–328PubMedCentralPubMedCrossRef

Wöhr M, Borta A, Schwarting RKW (2005) Overt behavior and ultrasonic vocalization in a fear conditioning paradigm: a dose–response study in the rat. Neurobiol Learn Mem 84:228–240PubMedCrossRef

Wohr M, Houx B, Schwarting RKW, Spruijt B (2008) Effects of experience and context on 50-kHz vocalizations in rats. Physiol Behav 93:766–776PubMedCrossRef

Womersley JS, Hsieh JH, Kellaway LA, Gerhardt GA, Russell VA (2011) Maternal separation affects dopamine transporter function in the spontaneously hypertensive rat: an in vivo electrochemical study. Behav Brain Funct BBF 7:1–11CrossRef

Wright JM, Gourdon JC, Clarke PBS (2010) Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: effects of amphetamine and social context. Psychopharmacology 211:1–13

Zafar HM, Paré WP, Tejani-Butt SM (1997) Effect of acute or repeated stress on behavior and brain norepinephrine system in Wistar-Kyoto (WKY) rats. Brain Res Bull 44:289–295PubMedCrossRef

Zhang HT, Whisler LR, Huang Y, Xiang Y, O’Donnell JM (2009) Postsynaptic alpha-2 adrenergic receptors are critical for the antidepressant-like effects of desipramine on behavior. Neuropsychopharmacology 34:1067–1077PubMedCentralPubMedCrossRef

Zhao Z, Baros AM, Zhang HT, Lapiz MD, Bondi CO, Morilak DA, O’Donnell JM (2008) Norepinephrine transporter regulation mediates the long-term behavioral effects of the antidepressant desipramine. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 33:3190–3200CrossRef

Title: Changes in behavior and ultrasonic vocalizations during antidepressant treatment in the maternally separated Wistar-Kyoto rat model of depression
Authors: P. J. van Zyl
J. J. Dimatelis
V. A. Russell
Publication date: 01-06-2014
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 2/2014
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-013-9463-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Changes in behavior and ultrasonic vocalizations during antidepressant treatment in the maternally separated Wistar-Kyoto rat model of depression

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2014

Episodic memory impairment in Addison’s disease: results from a telephonic cognitive assessment

Psychiatric disorders in individuals with methamphetamine dependence: prevalence and risk factors

Bridging the Gap: establishing the necessary infrastructure and knowledge for teaching and research in neuroscience in Africa

A comparison of spectral quality in magnetic resonance spectroscopy data acquired with and without a novel EPI-navigated PRESS sequence in school-aged children with fetal alcohol spectrum disorders

Erratum to: Episodic memory impairment in Addison’s disease: results from a telephonic cognitive assessment

Determinants of cognitive performance in children relying on cyanogenic cassava as staple food