The Orexin OX 2 Receptor-Dependent Pathway Is Implicated in the Development of Overactive Bladder and Depression in Rats Exposed to Corticosterone

• Published in: Neurourology and urodynamics 2025-01, Vol.44 (1), p.229
• Main Authors: Serefko, Anna, Wróbel, Jan, Szopa, Aleksandra, Dobrowolski, Piotr, Kluz, Tomasz, Wdowiak, Artur, Bojar, Iwona, Poleszak, Ewa, Romejko-Wolniewicz, Ewa, Derlatka, Paweł, Grabowska-Derlatka, Laretta, Kacperczyk-Bartnik, Joanna, Gieleta, Andrea Weronika, Bartnik, Paweł, Jakimiuk, Artur, Misiek, Marcin, Wróbel, Andrzej
• Format: Article
• Language: English
• Subjects: Animals; Corticosterone; Depression - drug therapy; Depression - metabolism; Depression - physiopathology; Disease Models, Animal; Male; Orexin Receptor Antagonists - pharmacology; Orexin Receptors - metabolism; Rats; Rats, Wistar; Signal Transduction - drug effects; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Urinary Bladder - physiopathology; Urinary Bladder, Overactive - chemically induced; Urinary Bladder, Overactive - drug therapy; Urinary Bladder, Overactive - metabolism; Urinary Bladder, Overactive - physiopathology; Urination - drug effects
• ISSN: 1520-6777

In the present study, we wanted to check whether TCS OX2 29 (TCS), a potent selective antagonist of OX2 receptors, would have positive effects in an animal model of detrusor overactivity co-existed with the depression-like state in Wistar male rats. The forced swim test with the measurement of spontaneous locomotor activity, conscious cystometry, determination of c-Fos expression in central micturition areas, and a set of biochemical analyses (with the use of urine, hippocampus, bladder urothelium, and detrusor muscle of tested animals) were carried out. The outcomes showed that a 7-day administration of TCS (3 mg/kg/day, subcutaneously) normalizes the cystometric parameters corresponding to overactivity of the detrusor and reverses the pro-depressive response. Furthermore, the antagonism of OX receptors restored the abnormal levels of overactive bladder markers (i.e., ATP, CGRP, OCT3, TRPV1, ROCK1, and VAChT), diminished neuronal overactivity in central micturition areas (i.e., pontine micturition center, ventrolateral periaqueductal gray, and medial preoptic area) as well as restored the altered hippocampal levels of CRF, cytokines (IL-1β, IL-6, IL-10, and TNF-α), and growth factors (BDNF and NGF) that reflected biochemical disturbances detected in depressed people. It seems that our findings open new perspectives regarding the implication of the orexin system in the functioning of the urinary bladder and in the pathophysiology of depression.