Mutant mouse models of depression: Candidate genes and current mouse lines

Urani, Alexandre; Chourbaji, Sabine; Gass, Peter

doi:10.1016/j.neubiorev.2005.03.020

Cited by 107 publications

(75 citation statements)

References 242 publications

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“…49 A downregulation of BDNF in the hippocampus, for example, is believed to correlate with depression-like behavior, and injections of BDNF into the hippocampus have been demonstrated to lead to decreased floating in the FST. 37 As we could recently demonstrate that endocannabinoid signaling via CB1 receptors regulates BDNF expression, 2,43 we investigated BDNF mRNA expression in the hippocampus of CB1 À/À and CB1 þ / þ mice.…”

Section: Discussionmentioning

confidence: 99%

Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice

et al. 2007

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Dysregulation of the endocannabinoid system is known to interfere with emotional processing of stressful events. Here, we studied the role of cannabinoid receptor type 1 (CB1) signaling in stress-coping behaviors using the forced swim test (FST) with repeated exposures. We compared effects of genetic inactivation with pharmacological blockade of CB1 receptors both in male and female mice. In addition, we investigated potential interactions of the endocannabinoid system with monoaminergic and neurotrophin systems of the brain. Naive CB1 receptor-deficient mice (CB1 À/À ) showed increased passive stress-coping behaviors as compared to wild-type littermates (CB1 þ / þ ) in the FST, independent of sex. These findings were partially reproduced in C57BL/6N animals and fully reproduced in female CB1 þ / þ mice by pharmacological blockade of CB1 receptors with the CB1 receptor antagonist SR141716. The specificity of SR141716 was confirmed in female CB1 À/À mice, where it failed to affect behavioral performance. Sensitivity to the antidepressants desipramine and paroxetine was preserved, but slightly altered in female CB1 À/À mice. There were no genotype differences between CB1 þ / þ and CB1 À/À mice in monoamine oxidase A and B activities under basal conditions, nor in monoamine content of hippocampal tissue after FST exposure. mRNA expression of vesicular glutamate transporter type 1 was unaffected in CB1 À/À mice, but mRNA expression of brain-derived neurotrophic factor (BDNF) was reduced in the hippocampus. Our results suggest that impaired CB1 receptor function promotes passive stress-coping behavior, which, at least in part, might relate to alterations in BDNF function.

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Section: Discussionmentioning

confidence: 99%

Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice

et al. 2007

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“…Many patients with severe major depressive episodes have dysregulated circadian cortisol control with significantly higher blood levels than healthy control subjects (Strickland et al, 2002;Urani et al, 2005). Elevated cortisol levels in depressed patients usually return to normal following successful antidepressant treatment (Wolkowitz et al, 1993(Wolkowitz et al, , 1999.…”

Section: Discussionmentioning

confidence: 99%

Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

Liu

Cai

et al. 2006

Neuropsychopharmacol

117

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g-Aminobutyric acid (GABA) transporter subtype 1 (GAT1), which transports extracellular GABA into presynaptic neurons, plays an important regulatory role in the function of GABAergic systems. However, the contributions of the GAT1 in regulating mental status are not fully understood. In this paper, we observed the behavioral alterations of GAT1 knockout (GAT1 À/À ) mice using several depressionand anxiety-related models (eg, the forced-swimming test and the tail-suspension test for testing depression-related behaviors; the openfield test, the dark-light exploration test, the emergence test, and the elevated plus maze (EPM) test for anxiety-related behaviors). Here we found that GAT1 À/À mice showed a lower level of depression-and anxiety-like behaviors in comparison to wild-type mice. Furthermore, GAT1 À/À mice exhibited measurable insensitivity to selected antidepressants and anxiolytics such as fluoxetine, amitriptyline, buspirone, diazepam, and tiagabine in the tail-suspension test and/or the EPM test. Moreover, the basal level of corticosterone was found to be significantly lower in GAT1 À/À mice. These results showed that the absence of GAT1 affects mental status through enhancing the GABAergic system, as well as modifying the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) activity in mice.

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“…Among many mutant mice lines generated, only a few can be regarded as simple genetic depression models or as useful models for elucidating the mechanism of action of antidepressants (Cryan and Mombereau, 2004;Urani et al, 2005). An example illustrating this notion are the data provided by Holmes et al (2002), who have studied antidepressant responses in 5-HTT knockout mice (5-HTT À/À ), and by , who have examined dopamine b-hydroxylase knockout (Dbh À/À ) mice, which are unable to synthesize NE and epinephrine.…”

Section: Discussionmentioning

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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Mutant mouse models of depression: Candidate genes and current mouse lines

Cited by 107 publications

References 242 publications

Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice

Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice

Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

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