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Basic Clin Pharmacol Toxicol ; 118(4): 249-58, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26381433

RESUMEN

Testicular torsion/detorsion (T/D) can induce depression in pre- and post-pubertal patients. This study was conducted to investigate the psychological impact of testicular torsion and mechanism underlying its depressive-like behaviour, as well as antidepressant-like activity of minocycline and possible involvement of nitric oxide (NO)/cyclic GMP pathway in this paradigm in male rats undergoing testicular T/D. Unilateral T/D was performed in 36 male adult Wistar rats, and different doses of minocycline were injected alone or combined with N(ω) -nitro-l-arginine methyl ester (l-NAME), non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), specific inducible NOS inhibitor; l-arginine, an NO precursor; and selective PDE5I, sildenafil. After assessment of locomotor activity in open-field test, immobility times were recorded in the forced swimming test (FST). Moreover, 30 days after testicular T/D, testicular venous testosterone and serum nitrite concentrations were measured. A correlation was observed between either a decrease in plasma testosterone or an increase in serum nitrite concentrations with prolongation in immobility time in the testicular T/D-operated rats FST. Minocycline (160 mg/kg) exerted the highest significant antidepressant-like effect in the operated rats in the FST (p < 0.001). Furthermore, combination of subeffective doses of minocycline (80 mg/kg) and either l-NAME (10 mg/kg) or AG (50 mg/kg) demonstrated a significant robust antidepressant-like activity in T/D group (p < 0.01). Consequently, NO/cGMP pathway was involved in testicular T/D-induced depressive-like behaviour and antidepressant-like activity of minocycline in the animal model. Moreover, a contribution was observed between either decreased testosterone or elevated serum nitrite levels and depressive-like behaviour following testicular T/D.


Asunto(s)
Antidepresivos/uso terapéutico , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Minociclina/uso terapéutico , Óxido Nítrico/metabolismo , Torsión del Cordón Espermático/complicaciones , Animales , Antidepresivos/administración & dosificación , GMP Cíclico/metabolismo , Depresión/etiología , Depresión/metabolismo , Modelos Animales de Enfermedad , Masculino , Minociclina/administración & dosificación , Actividad Motora/efectos de los fármacos , Nitritos/sangre , Ratas Wistar , Torsión del Cordón Espermático/metabolismo , Torsión del Cordón Espermático/psicología , Natación/psicología , Testosterona/sangre
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