Blebbistatin, a Myosin II Inhibitor, Exerts Antidepressant-Like Activity and Suppresses Detrusor Overactivity in an Animal Model of Depression Coexisting with Overactive Bladder

Overactive bladder (OAB) coexists with depression in women. Here, we assessed the effects of a 1-week treatment with blebbistatin, a myosin II inhibitor, on changes in behavior and detrusor overactivity (DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis-RA), with the aid of the forced swim test (FST), spontaneous locomotor activity test, and in vivo cystometric investigations in female Wistar rats. 13-cis-RA-induced depressive-like behavior and DO symptoms were associated with increased corticotropin-releasing factor (CRF) level in the plasma, prefrontal cortex (PFC), hippocampus (Hp), Barrington's nucleus (BN), and urinary bladder. Moreover, 13-cis-RA decreased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in plasma, PFC, Hp, and BN, while it increased BDNF and NGF levels in urinary bladder. Blebbistatin exerted antidepressant-like effect and attenuated changes in the cystometric parameters as well as the central and peripheral levels of CRF, BDNF, and NGF that were induced by 13-cis-RA, while it did not affect urine production, mean, systolic or diastolic blood pressure, or heart rate. The results point to blebbistatin as a potential treatment option for OAB coexisting with depression.

Neurotoxicity research. 2018 Aug 28 [Epub ahead of print]

Andrzej Wróbel, Urszula Doboszewska, Ewa Rechberger, Małgorzata Bańczerowska-Górska, Piotr Czuczwar, Ewa Poleszak, Jarosław Dudka, Piotr Wlaź, Paweł Miotła, Edyta Wlaźlak, Tomasz Rechberger

Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland. ., Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland. ., Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland., Gynaecological and Obstetrics Hospital in Wałbrzych, Paderewskiego 10, 58-301, Wałbrzych, Poland., Third Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland., Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland., Chair and Department of Toxicology, Medical University of Lublin, Chodźki 8, 20-093, Lublin, Poland., Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland., Clinic of Operative Gynecology and Gynecologic Oncology, 1st Department of Gynecology and Obstetrics, Medical University of Łódź, Wileńska 37, 94-029, Łódź, Poland.

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