Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats Role of serotonin synthesis
Autor: | Ido P. Kema, Marieke G. C. van der Hart, Anatoliy V. Gladkevich, Marit A. C. Tanke, Jakob Korf, Evelien Jagtman, Charmaine Y. Pietersen, Ben H.C. Westerink, Johan A. den Boer, Thomas I. F. H. Cremers, Minke E. Jongsma, Fokko J. Bosker |
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Přispěvatelé: | Groningen Research Institute of Pharmacy, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Lifestyle Medicine (LM), Medicinal Chemistry and Bioanalysis (MCB) |
Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Male
medicine.medical_specialty Microdialysis Serotonin Time Factors Efficacy Discontinuation Citalopram ANTIDEPRESSANT DISCONTINUATION PREPULSE INHIBITION EXTRACELLULAR SEROTONIN MONOAMINE SYNTHESIS Cellular and Molecular Neuroscience chemistry.chemical_compound Synthesis Internal medicine REUPTAKE INHIBITORS medicine Animals SSRI Rats Wistar Neurotransmitter Prepulse inhibition Brain Chemistry Depressive Disorder FLUORESCENCE DETECTION Behavior Animal Reactivity DORSAL HIPPOCAMPUS Cell Biology MAJOR DEPRESSION Turnover SELECTIVE SEROTONIN Rats Substance Withdrawal Syndrome Endocrinology chemistry Acoustic Startle Reflex MELANOMA PATIENTS Reuptake inhibitor Psychology Selective Serotonin Reuptake Inhibitors medicine.drug |
Zdroj: | Neurochemistry International, 57(8), 948-957. PERGAMON-ELSEVIER SCIENCE LTD |
ISSN: | 0197-0186 |
Popis: | We have investigated effects of continuous SSRI administration and abrupt discontinuation on biochemical and behavioral indices of rat brain serotonin function and attempted to identify underlying mechanismsBiochemistry of serotonin was assessed with brain tissue assays and microdialysis behavior was assessed as the acoustic startle reflexLong-term SSRI administration to rats reduced the content of 5-HT and its main metabolite shortly after inhibition of 5-HT synthesis in many brain areas with more than 50% Turnover was not appreciably decreased but significantly increased within 48 h of drug discontinuation The microdialysis experiments indicate that neuronal release of 5-HT depends strongly on new synthesis and emphasize the role of 5-HT1B receptors in the regulation of these processes Discontinuation of the SSRI rapidly increased behavioral reactivity to the external stimulus Additional startle experiments suggest that the increased reactivity is more likely related to the reduced extracellular 5-HT levels than to impaired synthesisThe combination of the marked reduction of serotonin content and limited synthesis may destabilize brain serotonin transmission during long-term SSRI treatment These combined effects may compromise the efficacy of an SSRI therapy and facilitate behavioral changes following non-compliance (C) 2010 Elsevier Ltd All rights reserved |
Databáze: | OpenAIRE |
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