[Ketoconazole antagonizes the immune and gonadotropic systems in the forced swimming test in male Wistar rats].
Disturbances in the activity of the corticotropic axis and immune system have been widely reported to be linked to the development of depression. The aim of this study was to explore the effects of ketoconazole, an imidazole derivative that inhibits gonadal and adrenal steroidogenesis, on changes in the total leukocyte count and the percentages of leukocyte subpopulations during the Porsolt forced swimming test (commonly used to measure the efficiency of antidepressants) in rats. Catheters were implanted in the carotid under general anesthesia, and blood samples (0.2 mL) were taken at 15 min intervals. Animals were allowed to move freely throughout the experiments. The levels of anxiety and locomotor activity were measured using the elevated plus-maze and open-field tests. Forced swimming induced changes in both the testosteronemia and the immune system, and these changes were inhibited by treatment with ketoconazole. An improvement (anxiolytic and antidepressant effects) in the behavioral response (elevated plus maze, forced swim) was also observed. These results suggest that the relationship between behavioral and physiological responses is multifactorial and that corticosterone plays a major role in the pathogenesis of psychiatric disorders.
Frih
Hacène
H
Laboratoire de neuroendocrinologie appliquée, Département de Biologie, Faculté des Sciences, Université Badji Mokhtar Annaba, B.P. 12, El Hadjar, Algérie.
Djenidi
Réda
R
Ali Rachedi
Bachir
B
Frih
Nabila
N
Tahraoui
Abdelkrim
A
Bairi
Abdel Majid
AM
D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000502:physiology; D007107:Immune System / Q000187:drug effects*; D007654:Ketoconazole / Q000494:pharmacology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000145:classification / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000097:blood*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D013739:Testosterone; D000324:Adrenocorticotropic Hormone; D007654:Ketoconazole; D003345:Corticosterone