Activity of litoxetine and other serotonin uptake inhibitors in the tail suspension test in mice

Perrault, Ghislaine; Morel, Éric; Živković, B.; Sanger, D. J.

doi:10.1016/0091-3057(92)90444-k

Cited by 62 publications

(31 citation statements)

References 15 publications

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“…5-HTT KO mice on the C57BL/6J background were used for these studies because the absence of baseline genotype differences in the tail suspension test facilitated interpretation of pharmacological effects. Consistent with previous reports, time spent immobile in the tail suspension test in ϩ/ϩ control mice was significantly reduced by acute administration of fluoxetine (Perrault et al 1992;Conti et al 2002). In marked contrast, 5-HTT Ϫ/Ϫ mice were completely insensitive to the anti-immobility effects of fluoxetine in this test.…”

supporting

confidence: 92%

“…Drug doses were 30 mg/kg fluoxetine, 20 mg/kg desipramine and 25 mg/kg imipramine. Doses were chosen on the basis of previous reports in mice of the anti-immobility effects of fluoxetine (Perrault et al 1992;Cesana et al 1993;Redrobe et al 1996;Eckeli et al 2000;Clenet et al 2001;Conti et al 2002), desipramine Vaugeois et al 1997;Srivastava and Nath 2000;Wong et al 2000;Clenet et al 2001;Cryan et al 2001;Lucki et al 2001;Conti et al 2002), and imipramine (Redrobe and Bourin 1997;Vaugeois et al 1997;Wong et al 2000;David et al 2001;Liu and Gershenfeld 2001;Do-Rego et al 2002).…”

Section: Drugsmentioning

confidence: 99%

“…These data show behavioral phenotypes in 5-HTT KO mice on the 129S6 background that are opposite in two putatively similar behavioral tests. Behavioral profiles in the tail suspension test and forced swim test are known to be affected by non-specific drug effects on motor function (Steru et al 1985;van der Heyden et al 1987;Perrault et al 1992;O'Neill and Conway 2001). A parsimonious explanation for increased forced swim test immobility in 129S6-background 5-HTT KO mice is that this effect resulted from a physical defect.…”

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confidence: 99%

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Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Holmes

Yang

Murphy

et al. 2002

Neuropsychopharmacology

263

181

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Inhibition of the serotonin transporter (5-HTT) is a principal initial target of many antidepressants. However, the contribution of the 5-HTT to their therapeutic efficacy is incompletely understood. We utilized a targeted gene mutation approach to examine the role of the 5-HTT in the behavioral actions of antidepressants. The 5-HTT mutation was bred onto two separate genetic backgrounds, C57BL/6J and 129S6. On a preliminary screen for gross physical, neurological and behavioral functions, all measures were normal with the exception that 5-HTT 5-HTT Ϫ / Ϫ mice on the C57BL/6J background showed no baseline antidepressant-related phenotype on either test. The behavioral effects of three antidepressants were tested in 5-HTT mutant mice (C57BL/6J background) in the tail suspension test. The anti-immobility effects of the serotonin reuptake inhibitor, fluoxetine (30 mg/kg), were abolished in 5-HTT Ϫ / Ϫ mice, confirming that the 5-HTT gene is required for the behavioral effects of fluoxetine. In contrast, 5-HTT Ϫ / Ϫ mice retained sensitivity to the anti-immobility effects of the norepinephrine reuptake inhibitor, desipramine (20 mg/kg), and the mixed serotonin/norepinephrine reuptake inhibitor, imipramine (25 mg/kg Antidepressants are thought to normalize the disturbances in monoamine function that occur in affective disorders (Feighner and Boyer 1996;Frazer 1997; Montgomery and Den Boer 2001). While dysfunctions in noradrenergic and dopaminergic systems are putative etiological factors in depression, there is considerable evidence indicating that perturbation of central serotonergic activity is a major etiological component of depression (Willner 1985;Murphy 1990;Maes and Meltzer 1995;Charney 1998 NO . 6 Antidepressant Responses in 5-HTT KO Mice 915 (for reviews see Brown and Linnoila 1990;Owens and Nemeroff 1998;Mann 1999). The serotonin transporter (5-HTT) acts as a key regulator of serotonin signaling. By regulating reuptake of released serotonin, the 5-HTT controls the duration and intensity of serotoninergic activity at the synapse. The 5-HTT has been directly implicated in depression by the finding that brain 5-HTT binding density is reduced in brains and platelets of depressed patients (e.g., Nemeroff et al. 1994;Malison et al. 1998;Mann et al. 2000). Moreover, a number of studies have found an association between genetic variation in the regulatory region of the 5-HTT gene and depression (e.g., Battersby et al. 1996; Collier et al. 1996a,b;Furlong et al. 1998;Rees et al. 1997;Menza et al. 1999; but see Seretti et al. 1999). The 5-HTT is also a major target for many antidepressant drug treatments (Blakely et al. 1991;Ramamoorthy et al. 1993). It is well known that the serotonin reuptake inhibitor (SRI) class of antidepressants increase concentrations of serotonin in the synapse by blocking the serotonin transporter (5-HTT) (Blakely et al. 1991;Ramamoorthy et al. 1993). However, given the time lag between the initial inhibitory effects of antidepressants on the 5-HTT and an observable improvement in sympt...

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supporting

confidence: 92%

Section: Drugsmentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Holmes

Yang

Murphy

et al. 2002

Neuropsychopharmacology

263

181

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“…Doses were chosen on the basis of previous reports in mice of the anti-immobility effects of reboxetine (Wong et al, 2000), desipramine (Lucki et al, 2001;Wong et al, 2000), imipramine (Bourin et al, 1998;Liu and Geshenfeld, 2003;Wong et al, 2000), and citalopram Perrault et al, 1992).…”

Section: Drugs and Drug Treatmentmentioning

confidence: 99%

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Dziedzicka-Wasylewska

Faron-Górecka

Kuśmider

et al. 2006

Neuropsychopharmacol

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One of the main theories concerning the mechanism of action of antidepressant drugs (ADs) is based on the notion that the neurochemical background of depression involves an impairment of central noradrenergic transmission with a concomitant decrease of the norepinephrine (NE) in the synaptic gap. Many ADs increase synaptic NE availability by inhibition of the reuptake of NE. Using mice lacking NE transporter (NET À/À ) we examined their baseline phenotype as well as the response in the forced swim test (FST) and in the tail suspension test (TST) upon treatment with ADs that display different pharmacological profiles. In both tests, the NET À/À mice behaved like wild-type (WT) mice acutely treated with ADs. Autoradiographic studies showed decreased binding of the b-adrenergic ligand [ 3 H]CGP12177 in the cerebral cortex of NET À/À mice, indicating the changes at the level of b-adrenergic receptors similar to those obtained with ADs treatment. The binding of [ 3 H]prazosin to a 1 -adrenergic receptors in the cerebral cortex of NET À/À mice was also decreased, most probably as an adaptive response to the sustained elevation of extracellular NE levels observed in these mice. A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by NET-inhibiting ADs such as reboxetine, desipramine, and imipramine. Citalopram, which is devoid of affinity for the NET, exerted a significant reduction of immobility time in the NET À/À mice. In the FST, reboxetine, desipramine, imipramine, and citalopram administered acutely did not reduce any further the immobility time shortened by NET knockout itself (ca 25%); however, antidepressant-like action of repeatedly (7 days) administered desipramine was observed in NET À/À mice, indicating that the chronic presence of this drug may also affect other neurochemical targets involved in the behavioral reactions monitored by this test. From the present study, it may be concluded that mice lacking the NET may represent a good model of some aspects of depression-resistant behavior, paralleled with alterations in the expression of adrenergic receptors, which result as an adaptation to elevated levels of extracellular NE.

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“…The frequency or duration of immobility is reduced by antidepressant treatments. The TST has been shown to be sensitive to an array of antidepressant treatments, including tricyclics, SSRIs, monoamine oxidase inhibitors, atypical antidepressants, and electroconvulsive therapy (Perrault et al, 1992;Steru et al, 1985Steru et al, , 1987Teste et al, 1990Teste et al, , 1993. Inbred rodent strains show substantial variability in baseline performance and behavioral response to antidepressant administration in the TST (Bai et al, 2001;Gershenfeld, 2001, 2003;Rippoll et al, 2003; for a review, see Cryan et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenomic Evaluation of the Antidepressant Citalopram in the Mouse Tail Suspension Test

Crowley

Brodkin

Blendy

et al. 2006

Neuropsychopharmacol

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The identification of genetic variants regulating antidepressant response in human patients would allow for more individualized, rational, and successful drug treatments. We have previously identified the BALB/cJ inbred mouse strain as highly responsive to the selective serotonin reuptake inhibitor (SSRI) citalopram in the tail suspension test (TST), a widely used and well-established screening paradigm for detecting compounds with antidepressant activity. In contrast, A/J mice did not show a significant response to citalopram in this test despite exposure to equivalent plasma levels of the drug. To identify genetic determinants of this differential response, 506 F 2 mice from an intercross between BALB/cJ and A/J mice were phenotyped. Composite interval mapping of 92 mice from the phenotypic extremes revealed three loci on chromosomes 7, 12, and 19 affecting citalopram response in the TST. The quantitative trait locus (QTL) at the telomeric end of chromosome 19 showed the greatest level of significance. Three candidate genes residing in this locus include those for vesicular monoamine transporter 2 (VMAT2, slc18a2), alpha 2A adrenergic receptor (adra2a), and beta 1 adrenergic receptor (adrb1). The protein coding regions of these three genes in BALB/cJ and A/J mice were sequenced and two polymorphisms were found in VMAT2 (Leu117Pro and Ser505Pro), while the transcribed regions of adra2a and adrb1 were of identical sequence between strains. Follow-up studies are needed to determine if the VMAT2 polymorphisms are functional and if they could explain the chromosome 19 QTL. The present quantitative trait study suggests possible candidate genes for human pharmacogenetic studies of therapeutic responses to SSRIs such as citalopram.

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Activity of litoxetine and other serotonin uptake inhibitors in the tail suspension test in mice

Cited by 62 publications

References 15 publications

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Pharmacogenomic Evaluation of the Antidepressant Citalopram in the Mouse Tail Suspension Test

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