Repeated rat-forced swim test: Reducing the number of animals to evaluate gradual effects of antidepressants

Mezadri, Tatiana; Batista, Gabriel M. S.; Portes, A.C.; Marino–Neto, José; Oliveira, Cilene Lino de

doi:10.1016/j.jneumeth.2010.12.015

Cited by 83 publications

(69 citation statements)

References 15 publications

(63 reference statements)

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“…Because this test can be repeated (Mezadri et al, 2011), we used a cross-over design for treatment, allowing for within-animal repeated-measure analysis. In RC::PDq;Pet1-cre mice, we confirmed the absence of genotype effect upon Veh exposure (F(1,190) = 1.446, p = 0.2366, Figure 2G), and found an effect of treatment (F(1,190) = 7.420 p = 0.0097, Figure 2H).…”

Section: Resultsmentioning

confidence: 99%

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

Teissier

Chemiakine

Inbar³

et al. 2015

Cell Reports

166

140

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SUMMARY Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim-test, while inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphe and increased median raphe serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. We furthermore identify opposing consequences of dorsal versus median raphe serotonergic neuron inhibition on floating behavior, together suggesting that median raphe hyperactivity increases anxiety, while a low dorsal/median raphe serotonergic activity ratio increases depression-like behavior. Thus we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphe function.

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Section: Resultsmentioning

confidence: 99%

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

Teissier

Chemiakine

Inbar³

et al. 2015

Cell Reports

166

140

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“…However, in earlier studies, the tricyclic antidepressant desipramine, the tetracyclic antidepressants maprotiline and mianserine and the norepinephrine–dopamine reuptake inhibitor nomifensine weren’t effective in rats which had not received the pretest session [162]. Antidepressant effects of fluoxetine treatment were detected at lower than the usual dose with several re-test sessions in the rat FST[49]. …”

Section: Test Design and Environmental Conditionsmentioning

confidence: 99%

Factors influencing behavior in the forced swim test

Bogdanova

Kanekar

D’Anci

et al. 2013

Physiology & Behavior

342

216

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The forced swim test (FST) is a behavioral test in rodents which was developed in 1978 by Porsolt and colleagues as a model for predicting the clinical efficacy of antidepressant drugs. A modified version of the FST added the classification of active behaviors into swimming and climbing, in order to facilitate the differentiation between serotonergic and noradrenergic classes of antidepressant drugs. The FST is now widely used in basic research and the pharmaceutical screening of potential antidepressant treatments. It is also one of the most commonly used tests to assess depressive-like behavior in animal models. Despite the simplicity and sensitivity of the FST procedure, important differences even in baseline immobility rates have been reported between different groups, which complicate the comparison of results across studies. In spite of several methodological papers and reviews published on the FST, the need still exists for clarification of factors which can influence the procedure. While most recent reviews have focused on antidepressant effects observed with the FST, this one considers the methodological aspects of the procedure, aiming to summarize issues beyond antidepressant action in the FST. The previously published literature is analyzed for factors which are known to influence animal behavior in the FST. These include biological factors, such as strain, age, body weight, gender and individual differences between animals; influence of preconditioning before the FST: handling, social isolation or enriched environment, food manipulations, various kinds of stress, endocrine manipulations and surgery; schedule and routes of treatment, dosage and type of the drugs as well as experimental design and laboratory environmental effects. Consideration of these factors in planning experiments may result in more consistent FST results.

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“…1). Time between the tests was at least 2 weeks, so as to avoid any previous forced swimming experience to affect an animal’s performance (De Pablo et al, 1989; Mezadri et al, 2011). The test consisted of a single 5-minute-long session in a tank filled with water at 22°-25°C.…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

Galanin contributes to monoaminergic dysfunction and to dependent neurobehavioral comorbidities of epilepsy

Medel-Matus

Shin

Sankar

et al. 2017

Experimental Neurology

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Status epilepticus (SE) in rats, along with chronic epilepsy, leads to the development of behavioral impairments resembling depressive disorder and/or attention deficit/hyperactivity disorder (ADHD), thus reflecting respective comorbidities in epilepsy patients. Suppressed neurotransmitter tone in the raphe nucleus (RN)-prefrontal cortex (PFC) serotonergic pathway and in the locus coeruleus (LC)-PFC noradrenergic pathway underlies depressive- and impulsive- like behavioral deficits respectively. We examined possible mechanisms leading to the monoamine dysfunction in brainstem efferents, namely modulatory effects of the neuropeptide galanin on serotonin (5-HT) and norepinephrine (NE) signaling. SE was induced in young adult male Wistar rats by LiCl and pilocarpine. Epileptic rats were categorized vis-à-vis behavioral deficits as not impaired, “depressed” and “impulsive”. Depressive- and impulsive- like behaviors were examined in the forced swimming test (FST). The strength of serotonergic transmission in RN-PFC and of noradrenergic transmission in LC-PFC was analyzed using in vivo fast scan cyclic voltammetry. Galanin receptor type 1 (GalR1) / type 2 (GalR2) antagonist M40, and a preferential GalR2 antagonist M871 were administered over 3 days locally into either RN or LC by means of ALZET osmotic minipumps connected to locally implanted infusion cannulas. Intra-RN injection of M40 improved serotonergic tone and depressive-like behavior in epileptic “depressed” rats. Intra-LC injection of M40 improved noradrenergic tone and impulsive-like behavior in epileptic “impulsive” rats. The effects of M40 were only observed in impaired subjects. The treatment did not modify neurotransmission and behavior in naïve and epileptic not impaired rats; in “depressed” rats the effects were limited to serotonergic transmission and immobility, while in “impulsive” rats – to noradrenergic transmission and struggling behavior. Intra-RN administration of M871 exacerbated depressive-like behavior, but had no effects on any other of the examined parameters in any category of animals. These findings suggest that endogenous galanin, acting through GalR1 may be involved in the pathophysiology of epilepsy-associated depression and ADHD via inhibiting RN-PFC serotonergic and LC-PFC noradrenergic transmissions respectively.

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Repeated rat-forced swim test: Reducing the number of animals to evaluate gradual effects of antidepressants

Cited by 83 publications

References 15 publications

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

Factors influencing behavior in the forced swim test

Galanin contributes to monoaminergic dysfunction and to dependent neurobehavioral comorbidities of epilepsy

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