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Escitalopram alters local expression of noncanonical stress-related neuropeptides in the rat brain via NPS receptor signaling

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Abstract

Background

Neuropeptide S (NPS) is a multifunctional regulatory factor that exhibits a potent anxiolytic activity in animal models. However, there are no reports dealing with the potential molecular relationships between the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs) and NPS signaling, especially in the context of novel stress-related neuropeptides action. The present work therefore focused on gene expression of novel stress neuropeptides in the rat brain after acute treatment with escitalopram and in combination with neuropeptide S receptor (NPSR) blockade.

Methods

Studies were carried out on adult, male Sprague–Dawley rats that were divided into five groups: animals injected with saline (control) and experimental rats treated with escitalopram (at single dose 10 mg/kg daily), escitalopram and SHA-68, a selective NPSR antagonist (at a single dose of 40 mg/kg), SHA-68 alone and corresponding vehicle (solvent SHA-68) control. To measure anxiety-like behavior and locomotor activity the open field test was performed. All individuals were killed under anaesthesia and the whole brain was excised. Total mRNA was isolated from homogenized samples of the amygdala, hippocampus, hypothalamus, thalamus, cerebellum, and brainstem. Real-time PCR was used for estimation of related NPS, NPSR, neuromedin U (NMU), NMU receptor 2 (NMUR2) and nesfatin-1 precursor nucleobindin-2 (NUCB2) gene expression.

Results

Acute escitalopram administration affects the local expression of the examined neuropeptides mRNA in a varied manner depending on brain location. An increase in NPSR and NUCB2 mRNA expression in the hypothalamus and brainstem was abolished by SHA-68 coadministration, while NMU mRNA expression was upregulated after NPSR blockade in the hippocampus and cerebellum.

Conclusions

The pharmacological effects of escitalopram may be connected with local NPSR-related alterations in NPS/NMU/NMUR2 and nesfatin-1 gene expression at the level of selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.

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Data availability statement

The datasets generated during and/or analysed during the following study: Aneta Piwowarczyk-Nowak, Artur Pałasz, Aleksandra Suszka-Świtek, Alessandra Della Vecchia, Aniela Grajoszek, Marek Krzystanek, John J. Worthington. Escitalopram alters local expression of noncanonical stress-related neuropeptides in the rat brain via NPS receptor signaling are available from the corresponding author on reasonable request.

Abbreviations

ACTH:

Adrenocorticotropic hormone

ARC:

Arcuate nucleus

B2M:

Beta-2-microglobulin

CNS:

Central nervous system

CRH/CRF:

Corticotrophin releasing hormone/ factor

DMH:

Dorsomedial hypothalamic nucleus

DMSO:

Dimethyl sulfoxide

Esc:

Escitalopram

EW:

Edinger–Westphal nucleus

ip:

Intraperitoneal

LC:

Locus coeruleus

NAc:

Nucleus accumbens

NMU:

Neuromedin U

NMUR2:

Neuromedin U receptor 2

NPS:

Neuropeptide S

NPSR:

Neuropeptide S receptor

NUCB2:

Nucleobindin 2

OFT:

Open field test

POMC:

Proopiomelanocortin

PVN:

Paraventricular nucleus

SCN:

Suprachiasmatic nucleus

SHA-68:

N-[(4-Fluorophenyl)methyl]tetrahydro-3-oxo-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxamide, 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide, neuropeptide S receptor antagonist

SON:

Supraoptic nucleus

SSRI:

Selective serotonin reuptake inhibitor

TRH:

Thyreotropin-releasing hormone

VMH:

Ventromedial hypothalamus

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Funding

This work was supported by the Medical University of Silesia grant for the Department of Histology No. PCN-1-011/K/0/O.

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Medical Sciences in Katowice, Medical University of Silesia, ul. Medyków 18, 40-752, Katowice, Poland

    Aneta Piwowarczyk-Nowak

  2. Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, ul. Medyków 18, 40-752, Katowice, Poland

    Artur Pałasz & Aleksandra Suszka-Świtek

  3. Section of Psychiatry, Department of Clinical and Experimental Medicine, University of Pisa, 67, Via Roma, 56100, Pisa, Italy

    Alessandra Della Vecchia

  4. Department for Experimental Medicine, Medical University of Silesia, ul. Medyków 4, 40-752, Katowice, Poland

    Aniela Grajoszek

  5. Department of Psychiatry and Psychotherapy, Faculty of Medical Sciences in Katowice, Clinic of Psychiatric Rehabilitation, Medical University of Silesia, ul. Ziolowa 45/47, 40-635, Katowice, Poland

    Marek Krzystanek

  6. Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, UK

    John J. Worthington

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  1. Aneta Piwowarczyk-Nowak
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  2. Artur Pałasz
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  4. Alessandra Della Vecchia
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Contributions

APN, AP, ADV: conceptualization, investigation, data curation, writing—original draft. APN, AP, ASS: Methodology, immunohistochemistry, tissue acquisition. ADV, AG: resources. AP, MK, JJW: formal analysis, corrections.

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Correspondence to Artur Pałasz.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Piwowarczyk-Nowak, A., Pałasz, A., Suszka-Świtek, A. et al. Escitalopram alters local expression of noncanonical stress-related neuropeptides in the rat brain via NPS receptor signaling. Pharmacol. Rep 74, 637–653 (2022). https://doi.org/10.1007/s43440-022-00374-z

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  • DOI: https://doi.org/10.1007/s43440-022-00374-z

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