Reboxetine attenuates forced swim test-induced behavioural and neurochemical alterations in the rat

The forced swim test is a behavioural paradigm that is predicative of antid epressant activity in rodents. Until recently, research has focused on the ability of antidepressant drugs to decrease immobility in the forced swim t est paradigm, but the neurochemical sequelae induced by swim stress, or the neurochemical basis of antidepressant-induced behavioural changes have rec eived little attention. In this regard, we have recently demonstrated that forced swim test exposure increases serotonergic activity in the amygdala, frontal cortex and hippocampus and dopamine turnover in the striatum. In ad dition, forced swim test-exposure activates the hypothalamic pituitary adre nal axis. The purpose of the present study was to examine the effect of tre atment with the selective noradrenaline reuptake inhibitor reboxetine (3, 1 0 and 30 mg/kg; i.p.) on immobility and defaecation scores in the forced sw im test, and on forced swim test-induced neurochemical and hypothalamic pit uitary adrenal axis changes in the rat. Reboxetine treatment (10 and 30 mg/ kg) significantly decreased immobility and defaecation in the forced swim t est in dose dependent manner. Furthermore, reboxetine produced a dose depen dent attenuation of forced swim test-induced increases in serotonin turnove r in the amygdala and frontal cortex and dopamine turnover in the striatum. Reboxetine (30 mg/kg) produced a modest, but non-significant, attenuation of forced swim test-induced increases in serum corticosterone concentration s. These data demonstrate that, in addition to the behavioural activity of reboxetine in the rat forced swim test paradigm, a dose-dependent attenuati on of swim stress-induced increases in serotonergic and dopaminergic activi ty occurred in a region specific manner. These are the first data to demons trate that treatment with the selective noradrenaline reuptake inhibitor, r eboxetine can impact on the activity of other neurotransmitter systems in r esponse to stress. Moreover, these data further demonstrate that this parad igm is a valuable tool in studying the effect of antidepressants, on both b ehaviour and swim stress-related alterations in central neurotransmitter fu nction and hypothalamic pituitary adrenal axis activity in the rat. (C) 199 9 Elsevier Science B.V. All rights reserved.