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Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

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Abstract

Rationale

A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. However, the neurochemical rationale behind this strategy needs to be further clarified.

Objectives

We examined the effect of chronic citalopram and subchronic lithium, alone or in combination, on (a) serum levels of citalopram and lithium, (b) animal behaviour and (c) hippocampal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. Furthermore, we examined the serum level of citalopram and hippocampal 5-HT following one acute citalopram injection.

Methods

Microdialysis in the freely moving animals was used to determine hippocampal 5-HT and 5-HIAA. The animal behaviour was examined in the open field and forced swim test.

Results

We found that chronic administration of citalopram (20 mg/kg/24 h s.c.) significantly increased the 5-HT baseline relative to vehicle-treated rats. Addition of subchronic lithium (60 mmol/kg chow pellet p.o.) to chronic citalopram therapy further elevated the 5-HT levels. Moreover, we found acute citalopram (5 mg/kg s.c.) to increase the 5-HT level. The immobility time in the FST and the locomotion in the OF were unaffected by any treatments.

Conclusions

The present results support the assumption that increases in hippocampal 5-HT neurotransmission may be important in the augmentatory effect of lithium.

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Acknowledgements

This study was supported by grants from The Novo Nordisk Foundation (2000.12.07), Fonden til forskning af Sindslidelser (2001), Psykiatrisk Forskningsfond (5129.1), Fonden til Laegevidenskabens fremme (01217), Hede Nielsen Fonden (HNP-2001), Einar Geert-Jørgensen & hustrus Legat (1008529) and Max Wørzners mindelegat (58.884). We thank Karen Byrialsen and Uffe Villadsen for constructive comments and Bodil Schmidt for skillful technical assistance.

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Authors and Affiliations

  1. Institute for Basic Psychiatric Research, Department of Biological Psychiatry, 8240, Risskov, Denmark

    Gregers Wegener, Zhale Bandpey, Ida Louise Heiberg & Raben Rosenberg

  2. Centre for Clinical Pharmacology, University of Aarhus, 8000 , Aarhus C, Denmark

    Gregers Wegener

  3. Department of Neurochemistry, H. Lundbeck A/S, 2500 , Copenhagen Valby

    Arne Mørk

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  1. Gregers Wegener
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  2. Zhale Bandpey
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Correspondence to Gregers Wegener.

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Wegener, G., Bandpey, Z., Heiberg, I.L. et al. Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat. Psychopharmacology 166, 188–194 (2003). https://doi.org/10.1007/s00213-002-1341-6

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