Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats Role of serotonin synthesis

Fokko J. Bosker*, Marit A. C. Tanke, Minke E. Jongsma, Thomas I. F. H. Cremers, Evelien Jagtman, Charmaine Y. Pietersen, Marieke G. C. van der Hart, Anatoliy V. Gladkevich, Ido P. Kema, Ben H. C. Westerink, Jakob Korf, Johan A. den Boer

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

25 Citaten (Scopus)

Samenvatting

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 mechanisms

Biochemistry of serotonin was assessed with brain tissue assays and microdialysis behavior was assessed as the acoustic startle reflex

Long-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 synthesis

The 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

Originele taal-2English
Pagina's (van-tot)948-957
Aantal pagina's10
TijdschriftNeurochemistry International
Volume57
Nummer van het tijdschrift8
DOI's
StatusPublished - dec.-2010

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