Fluoxetine moderates amphetamine response in chronically stressed rats with high and low levels of positive affectivity

Abstract

High level of positive affectivity serves as a protective factor against adverse effects of stress and low positive affectivity increases vulnerability to mental disorders, i.e. mood disorders and drug abuse. In animal models, rat 50-kHz ultrasonic vocalizations index the level of positive affect, whereas there are stable, trait-like inter-individual differences in terms of vocalization activity. Previously, we have demonstrated that experience of chronic stress can suppress amphetamine-induced 50-kHz vocalizations, but only in animals with low levels of vocalization activity. In the present study it was tested, whether the chronic stress effect on USV activity is preventable with fluoxetine treatment. Male Wistar high (n=32) and low (n=30) 50-kHz vocalizing rats were subjected to 43-day chronic variable stress (CVS) regimen. On day 17 of the CVS, fluoxetine treatment was started, followed up by the 19-day amphetamine test with USV and locomotor data recording on the 1st, 10th and 19th day. Chronically stressed rats developed cross-sensitization between previous CVS regimen and repeated administration of amphetamine in both groups of HC, and also in fluoxetine-pretreated LC rats. Fluoxetine had a different effect in chronically stressed rats with high and low trait of positive affectivity. Fluoxetine pretreatment increased the frequency-modulated and trill calls in proportions in repeatedly amphetamine treated LC rats, but not in any other group. These findings suggest that fluoxetine treatment modulates the effect of chronic stress on the rewarding effects of amphetamine depending on inter-individual differences in positive affectivity.