Antidepressants promote formation of heterocomplexes of dopamine D2 and somatostatin subtype 5 receptors in the mouse striatum

Szafran-Pilch, Kinga; Faron-Górecka, Agata; Kolasa, Magdalena; Żurawek, Dariusz; Szlachta, Marta; Solich, Joanna; Kuśmider, Maciej; Dziedzicka-Wasylewska, Marta

doi:10.1016/j.brainresbull.2017.10.003

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…DUO92008, respectively). According to Szafran-Pilch et al ( 2017 ), brain sections of 5 μm thickness were used in PLA method. Antibodies, the same as used in immunohistochemistry, were dissolved in Antibody Diluent in concentration 1:100.…”

Section: Methodsmentioning

confidence: 99%

“…For development the cognitive deficit we used ketamine (KET) as tool substance, according to our previous publication which showed that CLZ dose-dependently reversed KET-induced cognitive deficits (Szlachta et al, 2017 ). The method of choice to study endogenous G-protein–coupled receptor (GPCR) interaction in the native tissue is the in situ proximity ligation assay (PLA; Trifilieff et al, 2011 ; Perreault et al, 2016 ; Borroto-Escuela et al, 2017b ; Szafran-Pilch et al, 2017 ). PLA was used to accurately visualize the heterodimers both in vitro and in ex vivo mouse brain.…”

Section: Introductionmentioning

confidence: 99%

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Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex

Szlachta

Kuśmider

Pabian

et al. 2018

Front. Mol. Neurosci.

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G-protein–coupled receptor (GPCR) heterodimers are new targets for the treatment of schizophrenia. Dopamine D2 receptors and serotonin 5-HT1A and 5-HT2A receptors play an important role in neurotransmission and have been implicated in many human psychiatric disorders, including schizophrenia. Therefore, in this study, we investigated whether antipsychotic drugs (clozapine (CLZ) and haloperidol (HAL)) affected the formation of heterodimers of D2–5-HT1A receptors as well as 5-HT1A–5-HT2A receptors. Proximity ligation assay (PLA) was used to accurately visualize, for the first time, GPCR heterodimers both at in vitro and ex vivo levels. In line with our previous behavioral studies, we used ketamine to induce cognitive deficits in mice. Our study confirmed the co-localization of D2/5-HT1A and 5-HT1A/5-HT2A receptors in the mouse cortex. Low-dose CLZ (0.3 mg/kg) administered repeatedly, but not CLZ at 1 mg/kg, increased the level of D2–5-HT1A and 5-HT1A–5-HT2A heterodimers in the mouse prefrontal and frontal cortex. On the other hand, HAL decreased the level of GPCR heterodimers. Ketamine affected the formation of 5-HT1A–5-HT2A, but not D2–5-HT1A, heterodimers.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex

Szlachta

Kuśmider

Pabian

et al. 2018

Front. Mol. Neurosci.

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“…Indeed, a comparable situation occurs for truncated pig SST 5 variants ( Durán-Prado et al, 2012a ). Heterodimerization of SST 5 with a GPCR from a different family, the dopamine receptor D2 (D 2 receptor), has also been reported ( Rocheville et al, 2000a ), and its potential pharmacological consequences in CNS are being explored ( Szafran et al, 2012 ; Szafran-Pilch et al, 2017 ). SST 5 formation of heteromers seems to be promiscuous as it has also shown to interact with the ghrelin receptor GHS-R1a, in a context enabling a fine, coordinated regulation of glucose-stimulated insulin secretion by SRIF and ghrelin ( Park et al, 2012 ).…”

Section: Somatostatin Receptormentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

et al. 2018

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Somatostatin, also known as somatotropin-release inhibitory factor, is a cyclopeptide that exerts potent inhibitory actions on hormone secretion and neuronal excitability. Its physiologic functions are mediated by five G protein–coupled receptors (GPCRs) called somatostatin receptor (SST)1–5. These five receptors share common structural features and signaling mechanisms but differ in their cellular and subcellular localization and mode of regulation. SST2 and SST5 receptors have evolved as primary targets for pharmacological treatment of pituitary adenomas and neuroendocrine tumors. In addition, SST2 is a prototypical GPCR for the development of peptide-based radiopharmaceuticals for diagnostic and therapeutic interventions. This review article summarizes findings published in the last 25 years on the physiology, pharmacology, and clinical applications related to SSTs. We also discuss potential future developments and propose a new nomenclature.

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“…Our previous studies have shown that D 2 R and sst 5 R heterodimers can be considered as potential mediators of the effect of antidepressants, as the heterodimerization of these receptors occurs in native brain tissue as well as in primary striatal neuronal cultures where receptors are expressed at physiological levels. Moreover, antidepressant drugs promote the formation of these heterocomplexes in the mouse striatum (Szafran-Pilch et al 2017). Chronic administration of antidepressants influences the release of both these neurotransmitters (Pallis et al 2009; Pallis et al 2006; Pallis et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Regulation of somatostatin receptor 2 in the context of antidepressant treatment response in chronic mild stress in rat

et al. 2018

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RationaleThe role of somatostatin and its receptors for the stress-related neuropsychiatric disorders has been widely raised. Recently, we have also demonstrated the involvement of somatostatin receptor type 2-sst2R and dopamine receptor type 2-D2R in stress.ObjectiveIn this context, we decided to find if these receptors are involved in response to antidepressant treatment in animal model of depression—chronic mild stress (CMS).MethodsHere, we report data obtained following 7-week CMS procedure. The specific binding of [125I]Tyr3-Octreotide to sst2R and [3H]Domperidone to D2R was measured in the rat brain, using autoradiography. Additionally, the level of dopamine and metabolites was measured in the rat brain.ResultsIn the final baseline test after 7 weeks of stress, the reduced consumption of sucrose solution was observed (controls vs the stressed animals (6.25 0.16 vs. 10.39 0.41; p < 0.05). Imipramine was administered for the next 5 weeks, and it reversed anhedonia in majority of animals (imipramine-reactive); however, in some animals, it did not (imipramine-non-reactive). Two-way repeated measures ANOVA revealed significant effects of stress and treatment and time interaction [F(16, 168) = 3.72; p < 0.0001], n = 10 per groups. We observed decreased binding of [125I]Tyr3-Octreotide in most of rat brain regions in imipramine non-reactive groups of animals. The decrease of D2R after stress in striatum and nucleus accumbens and no effect of imipramine were observed.In the striatum and prefrontal cortex, the significant role of stress and imipramine in dopamine levels was observed.ConclusionsThe results obtained in binding assays, together with dopamine level, indicate the involvement of sst2R receptors for reaction to antidepressant treatment. Besides, the stress context itself changes the effect of antidepressant drug.

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Antidepressants promote formation of heterocomplexes of dopamine D2 and somatostatin subtype 5 receptors in the mouse striatum

Cited by 8 publications

References 37 publications

Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex

Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

Regulation of somatostatin receptor 2 in the context of antidepressant treatment response in chronic mild stress in rat

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