Effects of acute and chronic administration of selective monoamine re-uptake inhibitors in the rat forced swim test

Abstract

The rat forced swim test (FST) is a model that is used extensively as a screening test for antidepressant activity. It has previously been reported that thorough analysis of behaviour in this model reveals two distinct types of active response — climbing and swimming — and that these are separately evoked by re-uptake inhibitors selective for noradrenaline (NA) and serotonin (5-HT), respectively. In the present study, utilising re-uptake inhibitors selective for NA, talsupram, and 5-HT, 5-chloro-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)- phthalan (Lu 10-134-C), we examined if this scoring technique could detect the antidepressant potential of a selective serotonin re-uptake inhibitor (SSRI), and whether re-uptake inhibitors selective for distinct monoamine systems induce exclusive behavioural responses. We also analysed if chronic antidepressant administration for three weeks was more effective than acute treatment. We found Lu 10-134-C (40 mg/kg; PO) to be behaviourally active in this paradigm. Although treatment with talsupram (40 mg/kg; PO) resulted solely in climbing behaviour, Lu 10-134-C induced both climbing and swimming behaviour. However, chronic pre-treatment with either re-uptake inhibitor (20 mg/kg; twice daily; PO) failed to augment the response observed with acute treatment. Similarly, chronic administration of either compound was without effect on the basal, or stress-induced, serum corticosterone concentrations or anterior pituitary (AP) preproopiomelanocorticotropin (POMC) mRNA expression. These results suggest that selective monoamine re-uptake inhibition produces distinct, but not necessarily exclusive, behavioural responses in the forced swim test.