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.
Highlights
The potential involvement of proopiomelanocortin (POMC), kisspeptin and Melanin-concentrating hormone (MCH) signalling in several brain functions, including the affective responses, anxiety mechanisms, memory consolidation, sleep generation and control of autonomic homeostasis has come into consideration
The expression of the POMC seemed to be initially restricted to hypothalamic nuclei, low POMC mRNA levels were detected in the limbic structures including the amygdala and hippocampus that suggest its unknown function in the brain affective mechanisms
There was previously suggested that selective serotonin reuptake inhibitors (SSRI) treatment may affect peptidergic signalling by a modulation of the corticotropin-releasing factor (CRF) pathway and hypothalamicpituitary adrenal (HPA) axis [5, 10]
Summary
The potential involvement of proopiomelanocortin (POMC), kisspeptin and MCH signalling in several brain functions, including the affective responses, anxiety mechanisms, memory consolidation, sleep generation and control of autonomic homeostasis has come into consideration. Neuropharmacology of these important, multifunctional neuropeptides is so far poorly investigated. The highest densities of MCHR1 expression were found in the nucleus accumbens (NAc), hippocampus, locus coeruleus, basolateral amygdala, and neocortex, suggesting an involvement of MCH signalling in the various brain functions [3]. Given all aforementioned features we decided to examine the POMC, kisspeptin, Kiss1-R and MCHR1 mRNA levels jointly
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