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1

The effect of chronic mild stress on the regulation memory by the limbic D1, D2, and D3 receptors in rats

100%
Papp M., Gruca P., Lason-Tyburkiewicz M., Tota K.
Acta Neurobiologiae Experimentalis
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2015
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tom 75
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nr Supl.
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.
2

Changes in alfa1-adrenergic receptor subtypes in the hippocampus of rats non-responding to imipramine treatment in the chronic mild stress model of depression

76%
Rafa-Zablocka K., Zelek-Molik A., Bielawski A., Gruca P., Lason-Tyburkiewicz M., Papp M., Nalepa I.
Acta Neurobiologiae Experimentalis
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2011
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tom 71
|
nr S
Despite many years of research on depression the mechanism of the disorder remains elusive. Many studies are focused on dysfunction of central monoaminergic systems and some evidence exist for the role of α1-adrenoceptor (α1-AR). There are three subtypes of this receptor - α1A, α1B and α1D, which are widely distributed in brain. The aim of this study was to assess the expression of all three α1-AR, both at the mRNA and at the protein level in the hippocampi of male Wistar rats, subjected to the chronic mild stress (CMS) procedure followed by treatment with antidepressant drug, imipramine (IMI). Five groups of animals were studied: sham-saline; stress-saline; sham-IMI; stress-IMIresponders and stress-IMI-non-responders. The latter included the stressed animals resistant to IMI treatment as indicated by anhedonia test. The mRNA level was measured using qRT-PCR and SybrGreen dye, and the protein level was assessed by Western blotting. We found that mRNA expression of all α1-AR subtypes was significantly elevated only in the IMI-non-responders group (α1A-AR by 76%; α1B-AR by 96%; α1D-AR by 50%, vs. shamsaline). Moreover, stress alone caused an increase in α1A-AR mRNA (by 41%) though the effect was statistically insignificant. Changes found in the protein level were less pronounced. The only difference between IMI-responders and non-responders was found in α1A receptor protein that was decreased by 73% vs IMIresponders. The level of α1D protein was elevated in all IMI treated groups (by about 79%, vs. sham-saline) and the change occurred independently on stress procedure. No change in the α1B protein was found. Our results indicate that although α1A-AR and α1D-AR are involved in mechanism of IMI action, only the α1A receptor seems to be engaged in the phenomenon of resistance to IMI treatment. Supported by a grant POIG.01.01.02-12-004/09-00 financed by European Regional Development Fund.
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