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      Cyclosporine A Affects Open Field Behavior in DA Rats

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          Abstract

          Since the introduction of Cyclosporine A (CsA) for immunosuppression in solid-organ transplantation, the rate of allograft rejection has decreased substantially. However, treatment with CsA induces neuropsychological complications in patients, including affective disorders such as anxiety, disorientation, depression, aggression, paranoia, and apathy. These CsA-induced affective side effects cannot be extensively studied in humans. Therefore, this study investigates the effects of intraperitoneal CsA (20 mg/kg) injections on the open-field behavior of male Dark Agouti (DA) rats 1, 6, 12, and 23 h after drug administration on 3 consecutive days. CsA induced an increase in emotionality in DA rats 6 h after injection, reflected by decreased ambulatory activity in the open field and increased defecation. In addition, a decrease in rearing activity was observed 12 h after CsA administration. These behavioral alterations are discussed in the view of changes in cytokine profiles induced by CsA.

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          Most cited references30

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          Tests for emotionality in rats and mice: a review.

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            Immune-neuro-endocrine interactions: facts and hypotheses.

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              Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A.

              Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response. In T lymphocytes these drugs disrupt an unknown step in the transmission of signals from the T-cell antigen receptor to cytokine genes that coordinate the immune response. The putative intracellular receptors for FK506 and cyclosporin are cis-trans prolyl isomerases. Binding of the drug inhibits isomerase activity, but studies with other prolyl isomerase inhibitors and analysis of cyclosporin-resistant mutants in yeast suggest that the effects of the drug result from the formation of an inhibitory complex between the drug and isomerase, and not from inhibition of isomerase activity. A transcription factor, NF-AT, which is essential for early T-cell gene activation, seems to be a specific target of cyclosporin A and FK506 action because transcription directed by this protein is blocked in T cells treated with these drugs, with little or no effect on other transcription factors such as AP-1 and NF-kappa B. Here we demonstrate that NF-AT is formed when a signal from the antigen receptor induces a pre-existing cytoplasmic subunit to translocate to the nucleus and combine with a newly synthesized nuclear subunit of NF-AT. FK506 and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit.
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                Author and article information

                Journal
                Pharmacology Biochemistry and Behavior
                Pharmacology Biochemistry and Behavior
                Elsevier BV
                00913057
                May 1998
                May 1998
                : 60
                : 1
                : 71-76
                Article
                10.1016/S0091-3057(97)00467-X
                9610926
                8c7f23d6-cb00-44a0-9104-c1324f56da92
                © 1998

                https://www.elsevier.com/tdm/userlicense/1.0/

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