Antidepressant-like effect of pramipexole in an inflammatory model of depression

Lieberknecht, Vicente; Cunha, Maurício P.; Junqueira, Stella Célio; Coelho, Igor dos Santos; Souza, Luiz Felipe de; Santos, Adair Roberto Soares; Rodrigues, Ana Lúcia S.; Dutra, Rafael C.; Dafre, Alcir Luiz

doi:10.1016/j.bbr.2016.11.007

Cited by 37 publications

(28 citation statements)

References 61 publications

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“…In our study, we highlighted pretreatment with PPX inhibited LPS-stimulated expression of TNF-α, IL-1β, and IL-6 in the VTA and NAc but not the mPFC. In agreement with our observation, a recent study also showed that repeated PPX treatment attenuated the LPS-induced levels of IL-1β increased in the hippocampus of mice ( Lieberknecht et al, 2017 ). Thus, we speculate that upregulation of D3R plays antidepressant roles via suppressing the activation of proinflammatory cytokines signaling in the brain.…”

Section: Discussionsupporting

confidence: 93%

The Dopamine Receptor D3 Regulates Lipopolysaccharide-Induced Depressive-Like Behavior in Mice

Wang

Jia

et al. 2018

International Journal of Neuropsychopharmacology

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BackgroundThe altered expression and function of dopamine receptor D3 (D3R) in patients and animal models have been correlated with depression disease severity. However, the morphological alterations and biological effects of D3R in the brain after inflammation-induced depressive-like behavior remain elusive.MethodsIn the present study, we ascertained the changes of D3R expression in the brain regions after depressive-like behavior induced by peripheral administration of lipopolysaccharide (LPS). Protein levels of proinflammatory cytokines, brain-derived neurotrophic factor (BDNF), and extracellular signal-regulated kinase (ERK1/2)-cAMP-response element-binding protein (CREB) signaling pathway after activation or inhibition of D3R in the brain of depressive mice were also investigated.ResultsLPS caused a significant reduction of D3R in the ventral tegmental area (VTA), medial prefrontal cortex (mPFC), and nucleus accumbens (NAc), which are areas related to the mesolimbic dopaminergic system. Pretreatment with pramipexole (PPX), a preferential D3R agonist, showed antidepressant effects on LPS-induced depression-like behavior through preventing changes in LPS-induced proinflammatory cytokines (tumour necrosis factor-α, interleukin-1β, and interleukin-6), BDNF, and ERK1/2-CREB signaling pathway in the VTA and NAc. In opposition, treatment with a D3R selective antagonist NGB 2904 alone made mice susceptible to depression-like effects and caused changes in accordance with the LPS-induced alterations in proinflammatory cytokines, BDNF, and the ERK1/2-CREB signaling pathway in the mPFC and NAc.ConclusionsThese findings provide a relevant mechanism for D3R in LPS-induced depressive-like behavior via its mediation of proinflammatory cytokines and potential cross-effects between BDNF and the ERK1/2-CREB signaling pathway.

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Section: Discussionsupporting

confidence: 93%

The Dopamine Receptor D3 Regulates Lipopolysaccharide-Induced Depressive-Like Behavior in Mice

Wang

Jia

et al. 2018

International Journal of Neuropsychopharmacology

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“…Whilst several studies have demonstrated clinical efficacy of pramipexole treatment in depression, it is currently not known through which mechanisms the drug might bring about its antidepressant effects. Different mechanisms on different levels of neuroscientific description have been proposed, including activation and increased expression of dopamine receptors of the D2 subfamily [ 7 , 8 ], dopamine autoreceptor and dopamine transporter interaction [ 9 ], inhibition of NMDA receptors and/or NO-cGMP synthesis [ 7 ], increase in dopamine and serotonin neurotransmission [ 10 ], anti-inflammatory effects [ 11 ], changes in metabolism in certain brain regions [ 12 ], and inhibition of aversive information processing [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

An Experimental Medicine Investigation of the Effects of Subacute Pramipexole Treatment on Emotional Information Processing in Healthy Volunteers

et al. 2021

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Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing of emotional information in favour of positive relative to negative appraisal. In this study, we used an established experimental medicine assay to explore whether pramipexole treatment might have a similar effect. Employing a double-blind, parallel-group design, 40 healthy volunteers (aged 18 to 43 years, 50% female) were randomly allocated to 12 to 15 days of treatment with either pramipexole (at a peak daily dose of 1.0 mg pramipexole salt) or placebo. After treatment was established, emotional information processing was assessed on the neural level by measuring amygdala activity in response to positive and negative facial emotional expressions, using functional magnetic resonance imaging (MRI). In addition, behavioural measures of emotional information processing were collected at baseline and on drug, using an established computerized task battery, tapping into different cognitive domains. As predicted, pramipexole-treated participants, compared to those receiving placebo, showed decreased neural activity in response to negative (fearful) vs. positive (happy) facial expressions in bilateral amygdala. Contrary to our predictions, however, pramipexole treatment had no significant antidepressant-like effect on behavioural measures of emotional processing. This study provides the first experimental evidence that subacute pramipexole treatment in healthy volunteers modifies neural responses to emotional information in a manner that resembles the effects of conventional antidepressant drugs.

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“…The present study also showed that PPX signi cantly decreased the EAE-induced depressivelike behavior but did not affect the anhedonic-like behavior. Previous works have demonstrated that PPX exhibits promising responses for treatment-resistant depressed patients [85] and LPS-induced depressivelike behavior [41]. In the same way, a randomized trial compared PPX treatment with an established antidepressant (sertraline) in patients with Parkinson's disease (PD) without motor complications and identi ed that PPX ameliorated depression in PD [86].…”

Section: Discussionmentioning

confidence: 99%

“…Another way to assess the depressive-like behavior is the sucrose preference test (SPT), a reward-based test used as an indicator of anhedonia that consisted of giving two bottles of choice, one containing a sucrose solution (200 mL, 1%) and another one containing ltered tap water. First, each animal habituated to be housed individually and had access ad libitum to two bottles containing only tap water for 48 h. Then, one of the bottles was changed for a 1% sucrose solution for 24 h [41] and to avoid a place preference, the bottles were placed swapped after the rst 12 h. The bottles were weighed before and after the test to determine the amount of solution consumed, and the consumption was calculated as the percentage of sucrose solution consumed relative to the total amount of liquid drunk [42]. This behavioral method was adapted from Pazini et al (2017) [42].…”

Section: Forced Swimming Test (Fst) and Sucrose Preference Test (Spt)mentioning

confidence: 99%

“…Western blotting analysis was performed according to described by Lieberknecht et al [39,41]. The spinal cord, striatum, and inguinal lymph nodes samples were homogenized in ice-cold lysis buffer (50 mM Tris-HCl pH 7.5, 1 mM EDTA, 100 mM sodium uoride, 1 % protease inhibitor cocktail, 100 mM phenylmethylsulfonyl uoride, 2 mM sodium orthovanadate, 1 % Triton X-100, and 10 % glycerol).…”

Section: Western Blottingmentioning

confidence: 99%

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Dopaminergic Receptors as Neuroimmune Mediators in Experimental Autoimmune Encephalomyelitis

et al. 2021

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The dopaminergic system plays an essential role in maintaining homeostasis between the central nervous system (CNS) and the immune system. Previous studies have associated imbalances in the dopaminergic system with the pathogenesis of multiple sclerosis (MS). Herein, we investigate the protein levels of dopaminergic receptors (D1R and D2R) in different phases of the experimental autoimmune encephalomyelitis (EAE) model. We also examined if the treatment with pramipexole (PPX) -a dopamine D2/D3 receptor-preferring agonist -would be able to prevent the EAE-induced motor and mood dysfunction, as well as the underlying mechanisms of action. Our ndings showed that D2R immunocontent upregulated in the spinal cord of EAE mice 14 days post-induction. Moreover, D1R and D2R immunocontent was signi cantly increased in the lymph nodes during the chronic phase of EAE. Also, during this phase, oxidative damage in the spinal cord and striatum of EAE animals was signi cantly higher. During the pre-symptomatic phase, axonal damage in the spinal cord of EAE mice could already be found. In addition, PPX treatment failed to inhibit EAE progression and anhedonic-like behavior. Otherwise, PPX inhibited the depressive-like behavior. Relevantly, PPX oral treatment downregulated IL-1β levels and increased BNDF content in the spinal cord after EAE induction. Altogether, it is possible to conclude that D2R participates in crosstalk between CNS and immune system during autoimmune and neuroin ammatory response induced by EAE, mainly in the acute and chronic phase of the disease. Relevantly, a dopamine D2/D3 receptor-preferring agonist mitigated depressive-like behavior induced by EAE, which offers a new possibility for treating depressive symptoms in MS patients.

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Antidepressant-like effect of pramipexole in an inflammatory model of depression

Cited by 37 publications

References 61 publications

The Dopamine Receptor D3 Regulates Lipopolysaccharide-Induced Depressive-Like Behavior in Mice

The Dopamine Receptor D3 Regulates Lipopolysaccharide-Induced Depressive-Like Behavior in Mice

An Experimental Medicine Investigation of the Effects of Subacute Pramipexole Treatment on Emotional Information Processing in Healthy Volunteers

Dopaminergic Receptors as Neuroimmune Mediators in Experimental Autoimmune Encephalomyelitis

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