Abstract
Removal of the olfactory bulbs from the rodent induces neuronal reorganisation and the expression of behavioural, neurochemical, neuroendocrine and immune changes that resemble those observed in major depressive disorder. As such this model is widely used to examine the neurobiological substrates that may underlie the pathophysiology of depression and screen antidepressant agents. One of the most consistent changes observed in the olfactory bulbectomised (OB) mouse model is hyperactivity on exposure to a novel stressful environment. This behavioural response is attenuated selectively by chronic, but not acute, antidepressant treatment. This chapter provides a detailed protocol on the establishment of the OB mouse model and assessment of OB-related increase in locomotor activity in the open field test. Experimental variables which may impact on the results will be presented in addition to a short troubleshooting guide.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Willner P, Mitchell PJ (2002) The validity of animal models of predisposition to depression. Behav Pharmacol 13(3):169–188.
Cairncross KD, Cox B, Forster C, Wren AF (1977) The olfactory bulbectomized rat: a simple model for detecting drugs with antidepressant potential [proceedings]. Br J Pharmacol 61(3):497P.
Cairncross KD, King MG, Schofield SP (1975) Effect of amitriptyline on avoidance learning in rats following olfactory bulb ablation. Pharmacol Biochem Behav 3(6):1063–1067.
Kelly JP, Wrynn AS, Leonard BE (1997) The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 74(3):299–316.
Song C, Leonard BE (2005) The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev 29(4–5):627–647.
Calcagnetti DJ, Quatrella LA, Schechter MD (1996) Olfactory bulbectomy disrupts the expression of cocaine-induced conditioned place preference. Physiol Behav 59(4–5):597–604.
van Rijzingen IM, Gispen WH, Spruijt BM (1995) Olfactory bulbectomy temporarily impairs Morris maze performance: an ACTH(4–9) analog accelerates return of function. Physiol Behav 58(1):147–152.
Drevets WC (2000) Neuroimaging studies of mood disorders. Biol Psychiatry 48(8):813–829.
Sheline YI (2000) 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity. Biol Psychiatry 48(8):791–800.
Townsend JD, Eberhart NK, Bookheimer SY, Eisenberger NI, Foland-Ross LC, Cook IA, Sugar CA, Altshuler LL (2010) fMRI activation in the amygdala and the orbitofrontal cortex in unmedicated subjects with major depressive disorder. Psychiatry Res 183(3):209–217.
Wrynn AS, Mac Sweeney CP, Franconi F, Lemaire L, Pouliquen D, Herlidou S, Leonard BE, Gandon J, de Certaines JD (2000) An in-vivo magnetic resonance imaging study of the olfactory bulbectomized rat model of depression. Brain Res 879(1–2):193–199.
Shibata S, Watanabe S (1994) Facilitatory effect of olfactory bulbectomy on 2-deoxyglucose uptake in rat amygdala slices. Brain Res 665(1):147–150.
Mucignat-Caretta C, Bondi M, Caretta A (2004) Animal models of depression: olfactory lesions affect amygdala, subventricular zone, and aggression. Neurobiol Dis 16(2):386–395.
Nesterova IV, Gurevich EV, Nesterov VI, Otmakhova NA, Bobkova NV (1997) Bulbectomy-induced loss of raphe neurons is counteracted by antidepressant treatment. Prog Neuropsychopharmacol Biol Psychiatry 21(1):127–140.
Hozumi S, Nakagawasai O, Tan-No K, Niijima F, Yamadera F, Murata A, Arai Y, Yasuhara H, Tadano T (2003) Characteristics of changes in cholinergic function and impairment of learning and memory-related behavior induced by olfactory bulbectomy. Behav Brain Res 138(1):9–15.
Tadano T, Hozumi S, Yamadera F, Murata A, Niijima F, Tan-No K, Nakagawasai O, Kisara K (2004) Effects of NMDA receptor-related agonists on learning and memory impairment in olfactory bulbectomized mice. Methods Find Exp Clin Pharmacol 26(2):93–97.
Carlsen J, De Olmos J, Heimer L (1982) Tracing of two-neuron pathways in the olfactory system by the aid of transneuronal degeneration: projections to the amygdaloid body and hippocampal formation. J Comp Neurol 208(2):196–208.
Norrholm SD, Ouimet CC (2001) Altered dendritic spine density in animal models of depression and in response to antidepressant treatment. Synapse 42(3):151–163.
McNish KA, Davis M (1997) Olfactory bulbectomy enhances sensitization of the acoustic startle reflex produced by acute or repeated stress. Behav Neurosci 111(1):80–91.
Watanabe A, Tohyama Y, Nguyen KQ, Hasegawa S, Debonnel G, Diksic M (2003) Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic study. J Neurochem 85(2):469–475.
Grecksch G, Zhou D, Franke C, Schroder U, Sabel B, Becker A, Huether G (1997) Influence of olfactory bulbectomy and subsequent imipramine treatment on 5-hydroxytryptaminergic presynapses in the rat frontal cortex: behavioural correlates. Br J Pharmacol 122(8):1725–1731.
Leonard BE, Tuite M (1981) Anatomical, physiological, and behavioral aspects of olfactory bulbectomy in the rat. Int Rev Neurobiol 22:251–286.
Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157(1):115–118.
Ballmaier M, Narr KL, Toga AW, Elderkin-Thompson V, Thompson PM, Hamilton L, Haroon E, Pham D, Heinz A, Kumar A (2008) Hippocampal morphology and distinguishing late-onset from early-onset elderly depression. Am J Psychiatry 165(2):229–237.
Campbell S, Macqueen G (2004) The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci 29(6):417–426.
Romeas T, Morissette MC, Mnie-Filali O, Pineyro G, Boye SM (2009) Simultaneous anhedonia and exaggerated locomotor activation in an animal model of depression. Psychopharmacology (Berl) 205(2):293–303.
Stock HS, Ford K, Wilson MA (2000) Gender and gonadal hormone effects in the olfactory bulbectomy animal model of depression. Pharmacol Biochem Behav 67(1):183–191.
Frisch P, Bilkei-Gorzo A, Racz I, Zimmer A (2010) Modulation of the CRH system by substance P/NKA in an animal model of depression. Behav Brain Res 213(1):103–108.
Zukerman S, Touzani K, Margolskee RF, Sclafani A (2009) Role of olfaction in the conditioned sucrose preference of sweet-ageusic T1R3 knockout mice. Chem Senses 34(8):685–694.
Cain DP (1974) Olfactory bulbectomy: neural structures involved in irritability and aggression in the male rat. J Comp Physiol Psychol 86(2):213–220.
Kolunie JM, Stern JM (1995) Maternal aggression in rats: effects of olfactory bulbectomy, ZnSO4-induced anosmia, and vomeronasal organ removal. Horm Behav 29(4):492–518.
Liebenauer LL, Slotnick BM (1996) Social organization and aggression in a group of olfactory bulbectomized male mice. Physiol Behav 60(2):403–409.
Jaako-Movits K, Zharkovsky A (2005) Impaired fear memory and decreased hippocampal neurogenesis following olfactory bulbectomy in rats. Eur J Neurosci 22(11):2871–2878.
Ostrovskaya RU, Gruden MA, Bobkova NA, Sewell RD, Gudasheva TA, Samokhin AN, Seredinin SB, Noppe W, Sherstnev VV, Morozova-Roche LA (2007) The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer’s disease model. J Psychopharmacol 21(6):611–619.
Nakagawasai O, Hozumi S, Tan-No K, Niijima F, Arai Y, Yasuhara H, Tadano T (2003) Immunohistochemical fluorescence intensity reduction of brain somatostatin in the impairment of learning and memory-related behaviour induced by olfactory bulbectomy. Behav Brain Res 142(1–2):63–67.
Lumia AR, Teicher MH, Salchli F, Ayers E, Possidente B (1992) Olfactory bulbectomy as a model for agitated hyposerotonergic depression. Brain Res 587(2):181–185.
Chambliss HO, Van Hoomissen JD, Holmes PV, Bunnell BN, Dishman RK (2004) Effects of chronic activity wheel running and imipramine on masculine copulatory behavior after Âolfactory bulbectomy. Physiol Behav 82(4):593–600.
Primeaux SD, Holmes PV (1999) Role of aversively motivated behavior in the olfactory bulbectomy syndrome. Physiol Behav 67(1):41–47.
Stock HS, Hand GA, Ford K, Wilson MA (2001) Changes in defensive behaviors following olfactory bulbectomy in male and female rats. Brain Res 903(1–2):242–246.
Roche M, Shanahan E, Harkin A, Kelly JP (2008) Trans-species assessment of antidepressant activity in a rodent model of depression. Pharmacol Rep 60(3):404–408.
Zueger M, Urani A, Chourbaji S, Zacher C, Roche M, Harkin A, Gass P (2005) Olfactory bulbectomy in mice induces alterations in exploratory behavior. Neurosci Lett 374(2):142–146.
Jarosik J, Legutko B, Unsicker K, von Bohlen Und Halbach O (2007) Antidepressant-mediated reversal of abnormal behavior and neurodegeneration in mice following olfactory bulbectomy. Exp Neurol 204(1):20–28.
Cryan JF, Mombereau C (2004) In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9(4):326–357.
Bobkova NV, Nesteroval IV, Dana R, Dana E, Nesterov VI, Aleksandrova Y, Medvinskaya NI, Samokhin AN (2004) Morphofunctional changes in neurons in the temporal cortex of the brain in relation to spatial memory in bulbectomized mice after treatment with mineral ascorbates. Neurosci Behav Physiol 34(7):671–676.
Han F, Shioda N, Moriguchi S, Yamamoto Y, Raie AY, Yamaguchi Y, Hino M, Fukunaga K (2008) Spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101) treatment rescues olfactory bulbectomy-induced memory impairment by activating Ca2+/calmodulin kinase II and protein kinase C in mouse hippocampus. J Pharmacol Exp Ther 326(1):127–134.
Nakajima A, Yamakuni T, Haraguchi M, Omae N, Song SY, Kato C, Nakagawasai O, Tadano T, Yokosuka A, Mimaki Y, Sashida Y, Ohizumi Y (2007) Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice. J Pharmacol Sci 105(1):122–126.
Mucignat-Caretta C, Bondi M, Caretta A (2006) Time course of alterations after olfactory bulbectomy in mice. Physiol Behav 89(5):637–643.
Legutko B, Dudys D, Branski P, Znojek P, Pilc A (2006) Olfactory bulbectomy in C57BL/6J mice: behavioural deficits and effects of chronic citalopram treatment. FENS Forum Abstracts 3:A161:115.
Otmakhova NA, Gurevich EV, Katkov YA, Nesterova IV, Bobkova NV (1992) Dissociation of multiple behavioral effects between olfactory bulbectomized C57Bl/6J and DBA/2J mice. Physiol Behav 52(3):441–448.
Han F, Shioda N, Moriguchi S, Qin ZH, Fukunaga K (2008) The vanadium (IV) compound rescues septo-hippocampal cholinergic neurons from neurodegeneration in olfactory bulbectomized mice. Neuroscience 151(3):671–679.
Aleksandrova IY, Kuvichkin VV, Kashparov IA, Medvinskaya NI, Nesterova IV, Lunin SM, Samokhin AN, Bobkova NV (2004) Increased level of beta-amyloid in the brain of bulbectomized mice. Biochemistry (Mosc) 69(2):176–180.
Hellweg R, Zueger M, Fink K, Hortnagl H, Gass P (2007) Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas. Neurobiol Dis 25(1):1–7.
Licht CL, Kirkegaard L, Zueger M, Chourbaji S, Gass P, Aznar S, Knudsen GM (2010) Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice. Neurochem Int 56(4):603–610.
Bilkei-Gorzo A, Racz I, Michel K, Zimmer A (2002) Diminished anxiety- and depression-related behaviors in mice with selective deletion of the Tac1 gene. J Neurosci 22(22):10046–10052.
Mar A, Spreekmeester E, Rochford J (2000) Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat. Psychopharmacology (Berl) 150(1):52–60.
Wieronska JM, Papp M, Pilc A (2001) Effects of anxiolytic drugs on some behavioral consequences in olfactory bulbectomized rats. Pol J Pharmacol 53(5):517–525.
Saitoh A, Hirose N, Yamada M, Nozaki C, Oka T, Kamei J (2006) Changes in emotional behavior of mice in the hole-board test after olfactory bulbectomy. J Pharmacol Sci 102(4):377–386.
Kamei J, Hirose N, Oka T, Miyata S, Saitoh A, Yamada M (2007) Effects of methylphenidate on the hyperemotional behavior in olfactory bulbectomized mice by using the hole-board test. J Pharmacol Sci 103(2):175–180.
Gould TD, Doa DT, Kovacsis CE. (2009). The open field test. In Gould TD, editor Mood and Anxiety Related Phenotypes in Mice: characterization using behavioral tests. Humana Press, New York. p 1–21.
Slotkin TA, Miller DB, Fumagalli F, McCook EC, Zhang J, Bissette G, Seidler FJ (1999) Modeling geriatric depression in animals: Âbiochemical and behavioral effects of olfactory bulbectomy in young versus aged rats. J Pharmacol Exp Ther 289(1):334–345.
Lin EJ, Choi E, Liu X, Martin A, During MJ (2010) Environmental enrichment exerts sex-specific effects on emotionality in C57BL/6J mice. Behav Brain Res 10.1016/j.bbr.2010.08.019.
Gariepy JL, Rodriguiz RM, Jones BC (2002) Handling, genetic and housing effects on the mouse stress system, dopamine function, and behavior. Pharmacol Biochem Behav 73(1):7–17.
Mar A, Spreekmeester E, Rochford J (2002) Fluoxetine-induced increases in open-field habituation in the olfactory bulbectomized rat depend on test aversiveness but not on anxiety. Pharmacol Biochem Behav 73(3):703–712.
Sato A, Nakagawasai O, Tan-No K, Onogi H, Niijima F, Tadano T (2010) Effect of non-selective dopaminergic receptor agonist on disrupted maternal behavior in olfactory bulbectomized mice. Behav Brain Res 210(2):251–256.
Ostrovskaya RU, Retyunskaya MV, Bondarenko NA, Gudasheva TA, Bobkova NV, Samokhin AN (2005) Cholinopositive effect of dilept (neurotensin peptidomimetic) as the basis of its mnemotropic effect. Bull Exp Biol Med 139(3):340–344.
Sato A, Nakagawasai O, Tan-No K, Onogi H, Niijima F, Tadano T (2010) Influence of olfactory bulbectomy on maternal behavior and dopaminergic function in nucleus accumbens in mice. Behav Brain Res 215(1):141–145.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Roche, M. (2011). The Olfactory Bulbectomised Mouse. In: Gould, T. (eds) Mood and Anxiety Related Phenotypes in Mice. Neuromethods, vol 63. Humana Press. https://doi.org/10.1007/978-1-61779-313-4_17
Download citation
DOI: https://doi.org/10.1007/978-1-61779-313-4_17
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-312-7
Online ISBN: 978-1-61779-313-4
eBook Packages: Springer Protocols