Escitalopram as a modulator of proopiomelanocortin, kisspeptin, Kiss1R and MCHR1 gene expressions in the male rat brain

Abstract

Neuropeptides are important, multifunctional regulatory factors of the nervous system, being considered as a novel, atypical sites of antidepressants action. It has already been proven that some of them, such as selective serotonin reuptake inhibitors (SSRI), are able to affect peptidergic pathways in various brain regions. Despite these reports, there is so far no reports regarding the effect of treatment with SSRIs on brain proopiomelanocortin (POMC), kisspeptin, Kiss1R and MCHR1 gene expression. In the current study we examined POMC, kisspeptin, Kiss1R and MCHR1 mRNA expression in the selected brain structures (hypothalamus, hippocampus, amygdala, striatum, cerebellum and brainstem) of rats chronically treated with a 10 mg/kg dose of escitalopram using quantitative Real-Time PCR. Long-term treatment with escitalopram led to the upregulation of MCHR1 expression in the rat amygdala. Kisspeptin mRNA level was also increased in the amygdala, but Kiss1R mRNA expressions were elevated in the hippocampus, hypothalamus and cerebellum. POMC mRNA expressions were in turn decreased in the hippocampus, amygdala, cerebellum and brainstem. These results may support the hypothesis that these neuropeptides may be involved in the site-dependent actions of SSRI antidepressants. This is the first report of the effects of escitalopram on POMC, kisspeptin, Kiss1R and MCHR1 in animal brain. Our findings shed a new light on the pharmacology of SSRIs and may contribute to a better understanding of the alternative, neuropeptide-dependent modes of antidepressant action.

Modulatory effect of long-term treatment with escitalopram and clonazepam on the expression of anxiety-related neuropeptides: neuromedin U, neuropeptide S and their receptors in the rat brain

“…2). This finding appears to be in keeping with our previous results showing elevated proopiomelanocortin (POMC) and kisspeptin receptor Kiss1 mRNA levels in the rat hypothalamus after chronic escitalopram administration (Pałasz et al 2020). A distinct population of intensively NPS positive cells are observed almost exclusively within the brainstem (posterodorsal tegmental nucleus, locus coeruleus, parabrachial nucleus) and cerebellum (Purkinje cells and dentate nucleus).…”

Chronic treatment with escitalopram and venlafaxine affects the neuropeptide S pathway differently in adult Wistar rats exposed to maternal separation

“…NPSRs, which are the target proteins of NPS, are distributed in various serotonin-dependent areas [11] , [12] , [20] , which is why an effect on their modulation might have significance for the mechanism of action of escitalopram. Experimental studies have indicated that when escitalopram is given chronically, it alters the mRNA levels of various neuropeptides in the brainstem [26] , [27] , [91] and in the other brain structures [28] .…”

“…Escitalopram interacts with both the orthosteric and allosteric sites of the serotonin transporter (SERT) and enhances serotonin transmission, which is thought to be the basis for its therapeutic effects [25] . Recently, evidence that escitalopram alters the NPQ/SPX mRNA expression [26] , proopiomelanocortin (POMC) [27] and OX-A [28] was found in the rat hypothalamus. Venlafaxine is frequently used in the therapy of moderate-to-severe depression and generalized anxiety disorder and phobias [29] .…”

Current Perspectives on Kisspeptins Role in Behaviour

“…Given the interaction between kisspeptin and the serotonergic system, it is interesting to consider the brain regions involved in eliciting the antidepressant-like effects. In a recent study, adult male rats received four weeks of intraperitoneal escitalopram ( 92 ), a widely prescribed selective serotonin reuptake inhibitor for mood disorders, which increases serotonin activity in the brain by limiting its reabsorption. This experimental paradigm significantly upregulated Kiss1 mRNA expression in the amygdala (272% increase compared to saline treated rats).…”

“…This experimental paradigm significantly upregulated Kiss1 mRNA expression in the amygdala (272% increase compared to saline treated rats). Furthermore, Kiss1r mRNA was highly increased in the hypothalamus, hippocampus and cerebellum by 170%, 177% and 131%, respectively ( 92 ). Indeed, these findings are congruent with a previous study demonstrating that intra-cerebroventricular injections of serotonin hydrochloride to male rats significantly enhances hypothalamic kisspeptin expression and resultant circulating LH concentrations ( 93 ).…”