INTRODUCTION: The dopaminergic system plays an important role in regulating motivation and stress responses, which are impaired in depression. Wistar–Kyoto (WKY) rats are particularly sensitive to stress and are therefore often used as a model for affective disorders.

AIM(S):

METHOD(S): In this study, male WKY rats were subjected to chronic mild stress (CMS). During CMS, the animals received weekly ketamine (10 mg/kg, i.p.) or saline. Brains were collected 24 hours after the end of CMS and the last ketamine administration. The availability of dopamine D2 receptors was assessed by autoradiography using [3H]spiperone in selected brain regions, including the prefrontal cortex, striatum, nucleus accumbens (core and shell), hippocampus, substantia nigra, and amygdala.

RESULTS: Significant changes in D2 receptor binding were observed, which depended on both stress exposure and ketamine administration, as well as the brain region analysed. In some structures, chronic stress was associated with changes in D2 receptor availability, while in others, ketamine modified binding levels independently of stress. The greatest differences were observed in structures associated with motivation and reward regulation, particularly in the nucleus accumbens, especially its shell part. The obtained results indicate that the observed changes in D2 receptors are not only due to stress, but are the effect of the interaction between chronic stress and repeated exposure to ketamine.

CONCLUSIONS: This study demonstrates that in WKY rats, chronic stress and ketamine affect the dopaminergic system in a complex manner that depends on brain structure.

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