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

Piwowarczyk-Nowak, Aneta and Pałasz, Artur and Suszka-Świtek, Aleksandra and Della Vecchia, Alessandra and Grajoszek, Aniela and Krzystanek, Marek and Worthington, John J. (2022) Escitalopram alters local expression of noncanonical stress-related neuropeptides in the rat brain via NPS receptor signaling. Pharmacological reports : PR, 74 (4). pp. 637-653. ISSN 1734-1140

Text (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.