Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice

Iwai, Takashi; Ohnuki, Tomoko; Sasaki-Hamada, Sachie; Saitoh, Akiyoshi; Sugiyama, Azusa; Oka, Jun-Ichiro

doi:10.1016/j.bbr.2013.01.010

Cited by 28 publications

(14 citation statements)

References 27 publications

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“…A number of studies on treatment-resistant depression have also been carried out using other models, such as Flinders sensitive line (FSL) rats, CRCT1 2/2 mice, and adrenocorticotropic hormone administration (Kitamura et al, 2002;Iwai et al, 2013). FSL rats are one of the most studied "depressive" rat strains (Wegener et al, 2012).…”

Section: A Animal Models or Treatment-resistant Depressionmentioning

confidence: 99%

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International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

et al. 2018

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Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses and a major cause of morbidity worldwide. Currently available antidepressants are effective for most patients, although around 30% are considered treatment resistant (TRD), a condition that is associated with a significant impairment of cognitive function and poor quality of life. In this respect, the identification of the molecular mechanisms contributing to TRD represents an essential step for the design of novel and more efficacious drugs able to modify the clinical course of this disorder and increase remission rates in clinical practice. New insights into the neurobiology of TRD have shed light on the role of a number of different mechanisms, including the glutamatergic system, immune/inflammatory systems, neurotrophin function, and epigenetics. Advances in drug discovery processes in TRD have also influenced the classification of antidepressant drugs and novel classifications are available, such as the neuroscience-based nomenclature that can incorporate such advances in drug development for TRD. This review aims to provide an up-to-date description of key mechanisms in TRD and describe current therapeutic strategies for TRD before examining novel approaches that may ultimately address important neurobiological mechanisms not targeted by currently available antidepressants. All in all, we suggest that drug targeting different neurobiological systems should be able to restore normal function but must also promote resilience to reduce the long-term vulnerability to recurrent depressive episodes.

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Section: A Animal Models or Treatment-resistant Depressionmentioning

confidence: 99%

“…Chronic administration of adrenocorticotropic hormone in rats blocks the effects of antidepressants in the FST, alters monoamine response to stress, and downregulates HPA axis activity (Kitamura et al, 2002;Iwai et al, 2013;Walker et al, 2013a).…”

Section: A Animal Models or Treatment-resistant Depressionmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

et al. 2018

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“…Aberrant activation of the hypothalamic-pituitary adrenal (HPA) stress axis is commonly reported in both unipolar and bipolar depressed patients 2,3 and is associated with sub-optimal treatment responses, increased symptom severity, and poorer remission rates 3,4 . Chronic stimulation of the HPA axis via administration of adrenocorticotropic hormone-(1–24) (ACTH) blocks the immobility-reducing effects of imipramine in the forced swim test (FST) 5–9 , a well-established behavioral screen for antidepressant efficacy in rodents. Kitamura and colleagues 6 previously reported that lithium co-administration (100 mg/kg p.o.)…”

Section: Introductionmentioning

confidence: 99%

Insulin-stimulated mTOR activation in peripheral blood mononuclear cells associated with early treatment response to lithium augmentation in rodent model of antidepressant-resistance

et al. 2019

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Lithium has been shown to have some therapeutic efficacy as an adjunctive treatment for intractable forms of major depression. Activation of mammalian target of rapamycin (mTOR) and inhibition of glycogen synthase kinase-3β (GSK3β) have been implicated in its putative mechanisms of action. These proteins are integral components of the insulin signaling pathway, which may serve as a critical co-regulator of drug action. Utilizing an animal model of tricyclic antidepressant resistance, we investigated the relationship between insulin signaling and antidepressant response to lithium augmentation. Pre-treatment with adrenocorticotropic hormone (ACTH 100 µg/day i.p.) for 14 days effectively blocked the immobility-reducing effects of an acute dose of imipramine (10 mg/kg i.p.) in the forced swim test (FST). Lithium augmentation (100 mg/kg i.p.) rescued the antidepressant-like effects of imipramine in this model. Total and phosphorylated (p) levels of protein kinase B (Akt), mTOR, and GSK3β protein were quantified in the infralimbic cortex (ILPFC) following FST stress via Western blot. Levels of mTOR and pmTOR were further quantified in isolated peripheral blood mononuclear cells (PBMCs) following insulin stimulation (10 mg/mL for 5 min) via ELISA. Elevated levels of phosphorylated insulin signaling proteins were present in the ILPFC of ACTH-pretreated animals that received both imipramine and lithium, together with a concurrent increase in mTOR activation in PBMCs. Large correlations were observed between immobility time and insulin-stimulated mTOR levels in PBMCs. We propose that PBMC insulin challenge may be a useful probe for predicting antidepressant response to lithium administration, and potentially other therapies acting via similar mechanisms of action.

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“…As initially described by Kitamura and colleagues (Kitamura et al, 2002), chronic administration of ACTH(1–24) for 3, 7, or 14 days (100 μg/day) in rats blocked the antidepressant-like effects of imipramine and desipramine, whereas rats that received chronic vehicle treatment showed the expected antidepressant-induced reduction in immobility in the FST. These findings have been replicated using imipramine in rats (Walker et al, 2013a) and mice (Caldarone and Brunner, 2009; Iwai et al, 2013). It is unclear if chronic ACTH produces resistance to SSRIs, but these results provide support for chronic ACTH treatment as a model of TCA resistance.…”

Section: Identifying Treatment-resistance In Rodentsmentioning

confidence: 83%

Rodent models of treatment-resistant depression

Caldarone

Zachariou

King

2015

European Journal of Pharmacology

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Major depression is a prevalent and debilitating disorder and a substantial proportion of patients fail to reach remission following standard antidepressant pharmacological treatment. Limited efficacy with currently available antidepressant drugs highlights the need to develop more effective medications for treatment resistant patients and emphasizes the importance of developing better preclinical models that focus on treatment resistant populations. This review discusses methods to adapt and refine rodent behavioral models that are predictive of antidepressant efficacy to identify populations that show reduced responsiveness or are resistant to traditional antidepressants. Methods include separating antidepressant responders from non-responders, administering treatments that render animals resistant to traditional pharmacological treatments, and identifying genetic models that show antidepressant resistance. This review also examines pharmacological and non-pharmacological treatments regimes that have been effective in refractory patients and how some of these approaches have been used to validate animal models of treatment-resistant depression. The goals in developing rodent models of treatment-resistant depression are to understand the neurobiological mechanisms involved in antidepressant resistance and to develop valid models to test novel therapies that would be effective in patients that do not respond to traditional monoaminergic antidepressants.

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Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice

Cited by 28 publications

References 27 publications

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

Insulin-stimulated mTOR activation in peripheral blood mononuclear cells associated with early treatment response to lithium augmentation in rodent model of antidepressant-resistance

Rodent models of treatment-resistant depression

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