BACKGROUND AND AIMS: Stress plays a crucial role in the development of neuropsychiatric disorders, such as depression and schizophrenia. In animals, chronic stress impairs several brain systems, including dopaminergic (DA) neurotransmission. DA, apart from its involvement in the brain mechanisms of reward, regulates cognitive functions that are likewise disrupted in depression and schizophrenia. The impact of chronic stress on this regulation is, however, much less recognized. METHODS: One of the many models used in preclinical studies on the interaction between stress and human diseases is a chronic mild stress (CMS) procedure. In this model animals, subjected to a variety of mild stressors for a period of several weeks, develop impairments, which show striking similarity to symptoms of human depression and schizophrenia. The purpose of this project was to study the effect of intracranial injections of agonists and antagonists of D1, D2 and D3 on behaviour of control animals and stressed animals in the Novel Object Recognition (NOR) test. RESULTS: It was found that in the control animals a significant and dose-dependent improvement of the NOR behaviour was caused by D1 agonist SKF 81297 (0.05–0.75 µg) injected into prefrontal cortex (PFX), hippocampus (HPC) and nucleus accumbens septi (NAS), D2 agonist Quinpirole (0.1–5 µg) injected into PFX and HPC, and D3 antagonist SB 277-011 (0.1–1 µg) injected into PFX and HPC. The enhancement of novel object exploration induced by Quinpirole (1 and 5 µg) and SB 277-011 (0.5 and 1 µg), but not by SKF 81297 (0.2 and 0.5 µg), was substantially attenuated in animals subjected to the CMS procedure. CONCLUSIONS: These data provide evidence that the regulation of recognition memory by the limbic D2 and D3 receptors is under a potent influence of prolonged stress, and are discussed in terms of their implications for understanding the neurobiological mechanisms underlying pathology of affective and psychotic diseases.
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