Antidepressant-like Effects Induced by Chronic Blockade of the Purinergic 2X7 Receptor through Inhibition of Non-like Receptor Protein 1 Inflammasome in Chronic Unpredictable Mild Stress Model of Depression in Rats.

OBJECTIVE: Purinergic 2X7 receptor (P2X7R) activation is known to be involved in pathogenesis of depression. Our aims were to investigate P2X7R-activated inflammasome pathways in parallel with induction of depression and to test the antidepressant-like effects of the selective P2X7R antagonist Brilliant Blue G (BBG) in a rat model of chronic unpredictable mild stress (CUMS). METHODS: Male Wistar albino rats were divided into control, CUMS, CUMS＋BBG25 (25 mg/kg/day) and CUMS＋BBG50 (50 mg/kg/day) groups (n=10 for each group). Various stressors were applied to rats for 6 weeks to establish the CUMS model and daily BBG treatment was started at the end of 3rd week. Sucrose preference test and forced swim test (FST) were performed to assess antidepressant-like effects. Brain samples were obtained for real-time polymerase chain reaction and immunohistochemistry analysis. RESULTS: In FST, duration of immobility was reduced in the CUMS＋BBG50 group. Also, BBG treatment significantly enhanced sucrose preference. While NLRP3 gene expression levels were unchanged in rats exposed to the CUMS protocol, expression levels of other inflammasome pathway factors NLRP1, caspase-1, ASC, NF-κB, IL-1ß, IL-6 and P2X7R were increased. BBG treatment reduced expression levels of these factors. Likewise, Iba-1 and GFAP immunoreactivities were enhanced by the CUMS protocol and this action was reversed by BBG treatment. CONCLUSION: Chronic administration of BBG in CUMS model results in antidepressant-like activity in a dose dependent manner. Molecular and histological results show that these effects might be at least partially related to the suppression of inflammasome-related neuroinflammatory responses and suggest involvement of NLRP1 in depression.

Effects of silodosin, a selective alpha-1A adrenoceptor antagonist, on erectile function in a rat model of partial bladder outlet obstruction.

AIM: We investigated the effects of silodosin (selective α1A -adrenoceptor antagonist) on erectile dysfunction (ED) in a rat model of bladder outlet obstruction. METHODS: Adult male Sprague-Dawley rats (n = 32) were divided into four groups: (i) sham-operated control; (ii) silodosin-treated (sham) control (0.1 mg/kg/day); (iii) partial bladder outlet obstruction (PBOO); and (iv) silodosin-treated with PBOO. PBOO was induced by ligation of the urethra for 6 weeks. In vivo, erectile responses were monitored by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure (MAP). Organ-bath studies were performed on corpus cavernosum (CC) strips. Penises were assessed at baseline for protein expression of neuronal nitric oxide synthase (nNOS) and Rho-associated protein kinase (ROCK2) by Western blot. Immunohistochemistry and Masson trichrome staining were performed for analysis of nNOS protein levels and tissue alterations. RESULTS: The ratio of ICP/MAP was significantly decreased in obstructed rats (0.26 ± 0.043, P < 0.01) compared to sham-control rats (0.64 ± 0.10), which was restored by the treatment (0.59 ± 0.14, P < 0.01) compared with obstructed rats. Relaxation responses were significantly reduced in strips from the obstructed group. Silodosin restored nitrergic relaxant responses. nNOS expression in the obstructed group decreased, which was improved by treatment. The decreased smooth muscle/collagen ratio in the bladder obstructed group was reversed by the treatment. CONCLUSIONS: Silodosin improves erectile function in obstructed rats. Further clinical trials are needed to explore fully the potential benefits of silodosin in patients with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in association with ED. Neurourol. Urodynam. 36:597-603, 2017. © 2016 Wiley Periodicals, Inc.