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Delayed effects of antidepressant drugs in rats

Kuśmider, Maciej; Faron-Górecka, Agata; Dziedzicka-Wasylewska, Marta

doi: 10.1097/FBP.0b013e3280116ea2

The present study has addressed the question of what is more important for the occurrence of adaptive changes observed in the organism treated with antidepressant drugs: a daily dosing of the drug or the period of time necessary for the plastic events to develop. Here, we report on the effects of desipramine given to rats acutely (and tested following 2 drug-free weeks) as when the drug was administered repeatedly, on behavior in the forced swim test (i.e. significant shortening of immobility time by ca. 60%) and on the binding of [3H]CGP12177 to β-adrenergic receptors in the rat brain cortex (significant decrease of the binding by ca. 15%). Additionally, using the procedure of the repeated forced swim test (six times over 21 days), we show that the shortening of immobility time induced by a single dose of imipramine persisted throughout the whole experimental period and was similar to that seen in a group of animals treated repeatedly with the drug. Also, the effects of citalopram on immobility and climbing were similar after acute treatment and delayed testing to those seen after repeated drug exposure. The results obtained in the present study may question some conclusions that are usually drawn from the behavioral and, especially, biochemical studies concerning the need for repeated treatment with antidepressant drugs to induce various adaptive changes in the brain, which are thought to be responsible for the therapeutic efficacy of these drugs.

Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

Correspondence and requests for reprints to Professor Marta Dziedzicka-Wasylewska, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, PL-31-343 Kraków, Poland


Received 7 June 2006 Accepted as revised 31 July 2006

Citalopram used in this study was kindly provided by Lundbeck, Copenhagen, Denmark.

© 2006 Lippincott Williams & Wilkins, Inc.