Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.
Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required.
Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, PL, Poland. ksocala@op.pl.
Katarzyna
K
Socała
Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, PL, Poland.
Dorota
D
Nieoczym
Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, PL, Poland.
Mateusz
M
Pieróg
Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
Agnieszka
A
Szuster-Ciesielska
Department of Pharmacokinetics and Physical Pharmacy, Collegium Medicum, Jagiellonian University, Kraków, Poland.
Elżbieta
E
Wyska
Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, PL, Poland.
Piotr
P
Wlaź
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D013550:Swimming / Q000523:psychology; D016896:Treatment Outcome
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D000068677:Sildenafil Citrate
Acute stress; Corticosterone; Depression; Forced swim test; Reserpine; Sildenafil