Is the forced swimming test a suitable model for revealing antidepressant activity?

Borsini, Franco; Meli, Alberto

doi:10.1007/bf00176837

Cited by 951 publications

(513 citation statements)

References 95 publications

(153 reference statements)

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“…In both experimental paradigms, the animal is subjected to an inescapable stress and typically responds with alternating bouts of escape-oriented behavior and immobility. All major classes of ADs effectively reduce immobility in both tests, confirming their validity as drugscreening paradigms (Borsini and Meli, 1988;Cryan et al, 2005a;Petit-Demouliere et al, 2005;Porsolt, 2000;Steru et al, 1985). Drugs in both experimental paradigms are typically administered acutely.…”

Section: Introductionmentioning

confidence: 62%

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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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Section: Introductionmentioning

confidence: 62%

“…Drugs in both experimental paradigms are typically administered acutely. However, some studies have shown that subchronic or acute effects were increased by chronic pre-administration of the AD (Borsini and Meli, 1988;Conti et al, 2002;Dulawa et al, 2004).…”

Section: Introductionmentioning

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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“…Nevertheless, the FST does represent an acute stressful event, since it is associated with a profound increase in adrenocorticotropin and corticosterone levels (Bilang-Bleuel et al, 2002;Rittenhouse et al, 2002), as well as with neurochemical and morphological changes in the hippocampus (Bilang-Bleuel et al, 2005) and prefrontal cortex (Izquierdo et al, 2006). Importantly, the immobility response in the FST can be prevented by glucocorticoid antagonists (Jefferys and Funder, 1987;Korte et al, 1996;Bilang-Bleuel et al, 2005) and various types of antidepressant treatments, including tricyclic antidepressants, monoamine oxidase inhibitors, SSRIs, and NA reuptake inhibitors (see Borsini and Meli, 1988).…”

Section: Depression-like Behavior In Rats and The Fstmentioning

confidence: 99%

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Kuteeva

Wardi

Lundström

et al. 2008

Neuropsychopharmacol

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The present study on rat examined the role of galanin receptor subtypes in regulation of depression-like behavior as well as potential molecular mechanisms involved in the locus coeruleus (LC) and dorsal raphe (DR). The effect of intracerebroventricular (i.c.v.) infusion of galanin or galanin receptor GalR1-and GalR2-selective ligands was studied in the forced swim test, followed by quantitative in situ hybridization studies. Naive control, non-treated (swim control), saline-and fluoxetine-treated rats were used as controls in the behavioral and in situ hybridization studies. Subchronic treatment with fluoxetine reduced immobility and climbing time. Intracerebroventricular infusion of galanin, the GalR1 agonist M617 or the GalR2 antagonist M871 increased, while the GalR2(R3) agonist AR-M1896 decreased, immobility time compared to the aCSF-treated animals. Galanin also decreased the time of climbing. Galanin mRNA levels were upregulated by the combination of injection + swim stress in the saline-and the fluoxetine-treated groups in the LC, but not in the DR. Also tyrosine hydroxylase levels in the LC were increased following injection + swim stress in the saline-and fluoxetine-treated rats. Tryptophan hydroxylase 2 and serotonin transporter mRNAs were not significantly affected by any treatment. 5-HT 1A mRNA levels were downregulated following i.c.v. galanin, M617 or AR-M1896 infusion. These results indicate a differential role of galanin receptor subtypes in depression-like behavior in rodents: GalR1 subtype may mediate 'prodepressive' and GalR2 'antidepressant' effects of galanin. Galanin has a role in behavioral adaptation to stressful events involving changes of molecules important for noradrenaline and/or serotonin transmission.

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“…However, this animal model also has some drawbacks represented by the possibility to obtain some false positives or negatives. Drugs enhancing motor activity, such as anticholinergics and antihistamines, may give a ''false'' positive effect in the forced swimming test and antidepressants such as bupropion, nomifensine and amineptine would then be rejected since they increase motor activity (Borsini and Meli, 1988). Cytosolic Ca 2C regulates numerous neuronal functions (Berridge, 1998) and, therefore, a variation of intracellular Ca 2C contents can induce behavioural side effects.…”

Section: Discussionmentioning

confidence: 99%

Blockade of intracellular calcium release induces an antidepressant-like effect in the mouse forced swimming test

2006

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The role of intracellular calcium in the modulation of a depressant-like condition was investigated in the mouse forced swimming test. I.c.v. administration of TMB-8 (0.23e46.3 nmol per mouse), a blocker of Ca 2C release from intracellular stores, decreased the mouse immobility time. I.c.v. injection of thapsigargin (0.003e3 nmol per mouse), compound which selectively inhibits Ca 2C uptake into the endoplasmic reticulum, produced, 60 min after administration, a depressant-like condition. Xestospongin C (1e100 pmol per mouse i.c.v.), an InsP 3 -receptor antagonist, decreased the mouse immobility time. By contrast, D-myo-inositol (5.4e540 pmol per mouse i.c.v.), compound which produces InsP 3 , resulted in a depressant-like effect. Similarly, ryanodine (0.1e600 pmol per mouse i.c.v.), an RyR antagonist, decreased the immobility time values whereas the administration of 4-chloro-m-cresol (0.1e100 pmol per mouse i.c.v.), an RyR agonist, showed an opposite effect. The antidepressant-like effects observed with TMB-8, xestospongin C and ryanodine were comparable to that produced by the antidepressant drugs amitriptyline and clomipramine. The treatments employed did not produce any behavioural impairment of mice as revealed by the rota-rod and hole board tests indicating that the antidepressant-and depressant-like effects were not due to a compromised locomotor activity and spontaneous motility of the treated animals. These results indicate that a central variation in intracellular calcium contents is involved in the modulation of a depressive-like condition in the mouse forced swimming test. In particular, the blockade of both InsP 3 Rs and RyRs appears to play an important role in the induction of an antidepressant-like effect, whereas the stimulation of these receptors is involved in a depressant-like response of mice.

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Is the forced swimming test a suitable model for revealing antidepressant activity?

Abstract: The forced swimming test is reviewed. This test appears to be suitable for detecting antidepressant activity in rats but not in mice. Difference in experimental procedure may account for the different sensitivity to drugs of the two animal species.

Cited by 951 publications

References 95 publications

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Blockade of intracellular calcium release induces an antidepressant-like effect in the mouse forced swimming test

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