INTRODUCTION: Chronic mild stress (CMS) is commonly used to model anhedonia in rodents, but stress-sensitive strains may exhibit distinct temporal neurobiological responses. Wistar–Kyoto (WKY) rats are characterized by high stress reactivity and stable affective traits, making them suitable for studying the interaction of stress and antidepressant treatment over time.

AIM(S): Aim of the study was to determine whether repeated ketamine administration modulates time-dependent changes in serum brain-derived neurotrophic factor (BDNF) levels induced by CMS in stress-sensitive WKY rats and whether these changes relate to anhedonic behavior.

METHOD(S): Two independent cohorts of male WKY rats were subjected to the CMS protocol. During CMS, animals received weekly injections of ketamine or saline for 9–10 weeks. Anhedonia was assessed using a sucrose intake test. Serum BDNF levels were measured 24 or 48 hours after the last injection using ELISA and expressed relative to control values.

RESULTS: CMS consistently reduced sucrose consumption, confirming an anhedonic phenotype. Stress-related alterations in serum BDNF were observed only in saline-treated animals. After 24 hours, CMS decreased BDNF levels in stressed saline-treated rats, whereas no difference was observed in ketamine-treated group. After 48 hours however, CMS induced a significant increase in serum BDNF concentration in stressed and saline-treated rats. In contrast, BDNF levels in ketamine-treated animals did not differ from control values at both time points. A significant correlation between sucrose consumption and serum BDNF levels was observed only after 24 hours.

CONCLUSIONS: The results show that chronic stress causes changes in serum BDNF levels in WKY rats, and the nature of these changes depends on the time of measurement. Repeated ketamine administration prevents stress-induced changes in BDNF concentrations. Our results emphasize that the timing of measurement is crucial when interpreting peripheral neurotrophic markers in stress-sensitive animal models.

FINANCIAL SUPPORT: These studies were financed by statutory activities of the Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences in Kraków.