title: Modifications of anxiety-like behavior in prenatally stressed male offspring with imbalance of androgens.
abstract: Gonadal hormones have been well-known to affect brain regions known to be involved in the modulation of mood and affective-related behavior. Prenatal stress might alter hypothalamic-pituitary-gonadal axis, it could be a target for development of affective-related disorders in male offspring. The present study was designed to examine an anxiety-like behavior in the adult male offspring with low levels of endogenous androgens delivered from pregnant dams exposed to prenatal stress from gestation day 15 to gestation day 19. The non-stressed and prenatally stressed intact, gonadectomized (GDX) and GDX male offspring treated with oil solvent or testosterone propionate (TP, 0.5 mg/kg, s.c., 14 days, once daily) were used in all experiments. Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the open field test (OFT), respectively. Also, testosterone levels in the blood serum were measured in all experimental groups of offspring. Prenatally stressed GDX offspring demonstrated a significant decrease for time spent into the open arms and increase for time spent into the closed arms as compared to the non-stressed offspring. Administration of TP to the prenatally stressed GDX offspring resulted in a more markedly decrease of the time spent into the open arms and significantly raised the time spent into the closed arms as compared to the non-stressed GDX offspring treated with TP, non-stressed/prenatally stressed GDX offspring. Prenatally stressed GDX offspring showed a significant increase of crossing, rearing, grooming and defecation as compared to the prenatally stressed control offspring. On the contrary, administration of TP to the prenatally stressed GDX offspring significantly decreased crossing behavior, frequency of rearing and grooming behavior as compared to the non-stressed GDX offspring treated with TP, non-stressed/prenatally stressed GDX offspring. Prenatally stressed GDX offspring demonstrated a significant decrease of testosterone levels as compared to the non-stressed/prenatally stressed intact offspring, as well as non-stressed GDX offspring. Administration of TP significantly increased testosterone levels when prenatally stressed GDX offspring were compared with the prenatally stressed intact offspring, non-stressed/prenatally stressed GDX offspring. Thus, the results of the study clearly suggest that gonadectomy and TP supplementation profoundly changed an anxiety-related behavior in prenatally stressed male offspring in the EPM. Our current findings suggest that androgen deficiency in the prenatally stressed male offspring produces the high anxiety level and induces a marked anxious-like state. TP supplementation provokes development of profoundly anxious-like state in the prenatally stressed male offspring, Furthermore, this is the first study to show anxiogenic-like effect of TP administration on anxiety-related states in prenatally stressed male offspring with androgen deficiency.
authors.affiliation: Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology, Russian Academy of SciencesSt. Petersburg, Russia; Laboratory of Comparative Somnology and Neuroendocrinology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesSt. Petersburg, Russia; Department of Chemistry and Molecular Biology, ITMO UniversitySt. Petersburg, Russia.
authors.forename: Julia
authors.initials: J
authors.lastname: Fedotova
authors.affiliation: Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology, Russian Academy of Sciences St. Petersburg, Russia.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Akulova
authors.affiliation: Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology, Russian Academy of Sciences St. Petersburg, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pivina
authors.affiliation: 1st Department of Psychiatry, Faculty of Medicine, Pavol Jozef Safarik University and University Hospital Kosice, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Dragasek
authors.affiliation: 2nd Department of Internal Medicine, Faculty of Medicine, Comenius University Bratislava, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Caprnda
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical SciencesBrno, Czech Republic; 2nd Department of Surgery, Faculty of Medicine, Masaryk UniversityBrno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
keywords: Prenatal stress; anxiety; behavior; gonadectomy; male offspring; testosterone