Effects of immobilization stress on emotional behaviors in dopamine D3 receptor knockout mice

Xing, Bo; Liu, Peng; Jiang, Wenhui; Liu, Fei; Zhang, Hui; Cao, Guofen; Chen, Teng; Dang, Yonghui

doi:10.1016/j.bbr.2013.01.019

Cited by 27 publications

(14 citation statements)

References 39 publications

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“…D3 receptors in the PFC are located both post-synaptically on glutamatergic neurons and pre-synaptically on DA terminals, but a pre-synaptic inhibitory action on DA release appears to predominate, because D3 knockout animals have extracellular levels of DA that are double those seen in wild-type animals (Le Foll et al 2005 ; Song et al 2012 ). In several studies utilizing the forced swim test, these animals have been reported to display an antidepressant-like phenotype: relative to wild-type animals they were resistant to effects of repeated stress (Xing et al 2013 ) and more sensitive to antidepressant drugs (Leggio et al 2008 ); and both a knockout of D3 receptors and the D3 antagonist SB 277,011 prevented the effect of adolescent stress to increase immobility in adult animals (Seo and Kuzhikandathil 2015 ). Consistent with this picture, an antidepressant effect of the D3 antagonist/partial agonist cariprazine has been reported both in the CMS model (Papp et al 2014 ), and in randomized controlled trials of monotherapy for bipolar depression and adjunctive treatment in major depression (Durgam et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment`

et al. 2017

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Cognitive deficits in depression can be modelled using the novel object recognition (NOR) test, performance in which is impaired by chronic mild stress (CMS). We aimed to examine the involvement of mesocorticolimbic DA terminal regions, and to establish the substrate for CMS-induced impairment of NOR and its reversal by chronic antidepressant treatment. In experiments 1 and 2, we examined the effect of infusions into medial PFC, dorsal hippocampus (HPC), and nucleus accumbens (NAc) shell of D1 and D2 antagonists and D3 agonist, which were predicted to impair NOR with a short (1 h) delay, and of D1 and D2 agonists and D3 antagonist, which were predicted to facilitate NOR with a long (24 h) delay. Using optimal doses identified in experiment 2, in experiments 3 and 4, we examined effects on drug-stimulated NOR of CMS and chronic treatment with venlafaxine (VFX) or risperidone (RSP). We found a wide involvement of DA systems in memory for NOR: D1 receptors in PFC, HPC, and NAc; D3 receptors in PFC and HPC; and D2 receptors in PFC. CMS impaired D2- and D3-mediated effects in PFC and HPC; antidepressants rescued those effects in PFC but not HPC. The involvement of DA in NOR is multifaceted, but the effects of CMS and antidepressants are more discrete, involving D2 and D3 receptors in PFC specifically. While raising many difficult questions, these results suggest that the D2 and D3 receptors in the medial PFC may be an important substrate for cognitive deficits in depression and their remediation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-017-4651-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment`

et al. 2017

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“…Ritalin®) to children and rodents have been reported to result in the development of psychiatric disorders in adulthood [ 33 , 34 ]. Adult D3 receptor null mice have also been shown to be resistant to the behavioral dysfunction that results from immobilization stress [ 18 – 20 ]. The results of our current studies with D3 receptor null mice further underscore the critical role of D3 receptor in the etiology of the psychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Several D3 receptor ligands are being currently evaluated for treating depression [ 17 ]. Adult D3 receptor null mice have also been shown to be resistant to the behavioral dysfunction that results from immobilization stress [ 18 – 20 ]. Recently, D3 receptor was also shown to modulate anxiety-like behaviors and GABAergic neurotransmission in the lateral/basolateral amygdala [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Dopamine D3 Receptor Mediates Preadolescent Stress-Induced Adult Psychiatric Disorders

Seo

Kuzhikandathil

2015

PLoS ONE

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Several studies have shown that repeated stressful experiences during childhood increases the likelihood of developing depression- and anxiety-related disorders in adulthood; however, the underlying mechanisms are not well understood. We subjected drd3-EGFP and drd3-null mice to daily, two hour restraint stress episodes over a five day period during preadolescence (postnatal day 35 to 39), followed by social isolation. When these mice reached adulthood (post-natal day > 90), we assessed locomotor behavior in a novel environment, and assessed depression-related behavior in the Porsolt Forced Swim test. We also measured the expression and function of dopamine D3 receptor in limbic brain areas such as hippocampus, nucleus accumbens and amygdala in control and stressed drd3-EGFP mice in adulthood. Adult male mice subjected to restraint stress during preadolescence exhibited both anxiety- and depression-related behaviors; however, adult female mice subjected to preadolescent restraint stress exhibited only depression-related behaviors. The development of preadolescent stress-derived psychiatric disorders was blocked by D3 receptor selective antagonist, SB 277011-A, and absent in D3 receptor null mice. Adult male mice that experienced stress during preadolescence exhibited a loss of D3 receptor expression and function in the amygdala but not in hippocampus or nucleus accumbens. In contrast, adult female mice that experienced preadolescent stress exhibited increased D3 receptor expression in the nucleus accumbens but not in amygdala or hippocampus. Our results suggest that the dopamine D3 receptor is centrally involved in the etiology of adult anxiety- and depression-related behaviors that arise from repeated stressful experiences during childhood.

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“…ACCEPTED MANUSCRIPT (Chourbaji et al, 2008;Xing et al, 2013), though D3R -/ -appear more resistant to stressful procedures than WT littermates (Leggio et al, 2008;Xing et al, 2013), show better performance in the elevated plus maze and are more sensitive to the anxiolytic effect of diazepam (Leggio et al, 2011;Leggio et al, 2015). Finally, extensive evidence indicates that depression is accompanied by downregulation of Brain-Derived Neurotrophic Factor (BDNF) and that antidepressant drug treatments reestablish, at least in part, BDNF levels (Bjorkholm & Monteggia, 2016).…”

Section: Accepted Manuscriptmentioning

confidence: 95%

Current drug treatments targeting dopamine D3 receptor

Leggio

Bucolo

Platania

et al. 2016

Pharmacology & Therapeutics

129

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Effects of immobilization stress on emotional behaviors in dopamine D3 receptor knockout mice

Cited by 27 publications

References 39 publications

Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment`

Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment`

Dopamine D3 Receptor Mediates Preadolescent Stress-Induced Adult Psychiatric Disorders

Current drug treatments targeting dopamine D3 receptor

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