Is dopamine a limiting factor of the antidepressant-like effect in the mouse forced swimming test?

doi:10.1016/j.pnpbp.2004.06.010

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 28, Issue 8, December 2004, Pages 1255-1259

https://doi.org/10.1016/j.pnpbp.2004.06.010 Get rights and content

Abstract

To study the role of dopamine (DA) in antidepressant-like effect in the forced swimming test (FST), the relationship between the magnitude of the antidepressant-like effect of drugs [citalopram, fluoxetine, paroxetine (selective serotonin reuptake inhibitors), desipramine (tricyclic antidepressant), maprotiline (tetracyclic antidepressant), bupropion (DA reuptake inhibitor), and tranylcypromine (inhibitor of monoamine oxidase)] and the corresponding concentration of DA in the whole brain of mice was investigated. A trend for an inversely proportional linear relationship [(magnitude of the antidepressant-like effect)=−0.0145×(concentration of DA in the whole brain)+34.773 (r=0.276)] was observed between the magnitude of the antidepressant-like effect and the concentrations of DA in the whole brain, but this correlation was not significant. This result suggests that the high concentration of DA in the whole brain could be a limiting factor for the antidepressant-like effect of antidepressants such as tranylcypromine and seems to play a minor role in the antidepressant-like activity of another antidepressant such as bupropion in the FST.

Introduction

The implication of dopamine (DA) pathways in the pathogenesis of depression was suggested by various studies (Brown and Gershon, 1993). This role of DA is commonly based on the hypothesis that noradrenaline and/or serotonin and/or the DA system could be deficient in depression. In humans, this role was confirmed by the benefit of DA receptor agonist addition to standard antidepressants in the treatment of resistant depression (Takahashi et al., 2003). However, the efficacy of the combination of olanzapine, an atypical antipsychotic (DA receptor antagonist), and fluoxetine (a selective serotonin reuptake inhibitor) was also demonstrated in treatment-resistant depression (Thase, 2002). The 5-HT_2C antagonist activity of olanzapine, which could increase DA mesocorticolimbic function (Di Matteo et al., 2001), can be evoked accordingly to the monoamine deficiency hypothesis to explain this paradoxical result for a DA antagonist drug. Another explanation could be that an excessive DA transmission could be also deleterious in certain subtypes of depression. This hypothesis is consistent with clinical observation that the addition of 2.5–5 mg/day bromocriptine (DA receptor agonist) with imipramine improved the depressive symptoms of a patient with refractory depression, but that the clinical status returned to the original level when the dose was increased to 15 mg/day (Wada et al., 2001). The biochemical evidence of this hypothesis is difficult to obtain in humans, and an animal model of depression was used to investigate this hypothesis. The forced swimming test (FST) is a behavioural test considered as a model of depression and is used as a predictor of antidepressant activity in rodents (Porsolt et al., 1978). In a previous study, biochemical evidence indicating that the DA system played a role in the antidepressant-like effect observed in this test was found (Renard et al., 2003). To study the influence of an excessive DA transmission on the antidepressant activity, the relationship between DA concentrations in the whole brain and the magnitude of the antidepressant-like effects of drugs likely to change the DA concentration in the whole brain was tested in the FST.

Section snippets

Animals

Experiments were carried out on naive male Swiss mice (Janvier Breeding Center, France) weighing 20–24 g at the time of testing. All mice were housed at a constant room temperature (20±1 °C) in standard laboratory conditions, including free access to food and water. Each experimental group consisted of 10 randomly chosen mice. Mice were only used once during the testing period. All experimental procedures were in strict accordance with the guidelines of the French Ministry of Agriculture on the

Results

After the FST, bupropion [16 mg/kg; F(10, 99)=23.08, p≤0.01], citalopram [16 mg/kg; F(10, 99)=23.08, p≤0.01], desipramine [16 mg/kg; F(10, 99)=23.08, p≤0.01], fluoxetine [32 mg/kg; F(10, 99)=23.08, p≤0.01], maprotiline [16 mg/kg; F(10, 99)=23.08, p≤0.01], paroxetine [16 mg/kg; F(10, 99)=23.08, p≤0.01], and tranylcypromine [8 mg/kg; F(10, 99)=23.08, p≤0.01] significantly decreased the immobility time of mice in comparison with controls (Table 1). Buspirone (4 mg/kg) and diazepam (1 mg/kg) did

Discussion

According to a previous study, FST provoked a significant increase of the concentration of DA during the test, which confirms the interest of this test to investigate the relationship between the DA concentration in the brain and antidepressant effect (Renard et al., 2003). Antidepressant drugs were chosen in function of their affinity to each neurotransmitter system and their magnitude of antidepressant-like effect in the FST. As was reported in previous studies (Bourin et al., 1998, Bourin et

Conclusion

A high concentration of DA in the whole brain could be a limiting factor for the antidepressant-like effect of antidepressants such as tranylcypromine and seems to play a minor role in the antidepressant-like activity of another antidepressant such as bupropion in the FST. The limited correlation between DA concentration and the antidepressant-like effect could also be explained by the defects in the measurement of DA concentration (the concentrations of DA were measured in the whole brain and

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Citation Excerpt :
There was a significant correlation between the drug dose and effect size [r = 0.91, p = 0.04]. Three papers report the effects of bupropion in the FST using Swiss mice in the Bourin laboratory (Bourin et al., 2009; Bourin et al., 1998; Renard et al., 2004). The analysis of these studies shows a strong correlation between dose and effect size [r = 0.91, p = 0.012].
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We identified studies that examined effects of antidepressants in the FST in mice and used standard protocol, male mice and acute drug administration. We calculated Effect sizes using Cohen’s d, homogeneity using Q statistic and correlations using Pearson’s correlation.
Results indicate that all drugs reduce immobility in the FST. However, effect sizes for most drugs are heterogeneous and do not show a consistent dose/response relationship across variability factors. Reducing variability by examining only one strain or data from individual laboratories partially increases dose response relationship.
These findings suggest that whereas the FST is a valid tool to qualitatively screen antidepressant effects its validity in the context of hierarchical comparison between doses or compounds might be relevant only to single experiments.
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Is dopamine a limiting factor of the antidepressant-like effect in the mouse forced swimming test?

Abstract

Introduction

Section snippets

Animals

Results

Discussion

Conclusion

Prog. Neuro-psychopharmacol. Biol. Psychiatry

Trends Pharmacol. Sci.

Prog. Neuro-psychopharmacol. Biol. Psychiatry

Eur. J. Pharmacol.

Prog. Neuro-psychopharmacol. Biol. Psychiatry

Clonidine as a sensitising agent in the forced swimming test for revealing antidepressant activity

J. Psychiatry Neurosci.

Comparison of behavioural effects after single and repeated administrations of four benzodiazepines in three mice behavioural models

J. Psychiatry Neurosci.

Dopamine and depression

J. Neural Transm. Gen. Sect.