Effect of chronic variable stress on corticosterone levels and hippocampal extracellular 5-HT in rats with persistent differences in positive affectivity

Raudkivi K, Mallo T, Harro J. Effect of chronic variable stress on corticosterone levels and hippocampal extracellular 5-HT in rats with persistent differences in positive affectivity. Objective: The trait of experiencing positive affect could make a unique contribution to the pathogenesis of affective disorders. Animal models of positive emotionality are scarce but 50-kHz ultrasonic vocalizations (USVs) in rats have been associated with rewarding experience. We have previously reported that persistent inter-individual differences in expression of 50-kHz USVs (chirps) exist, and that male rats producing fewer 50-kHz USVs are more sensitive to chronic variable stress (CVS). In this study we examined the effect of CVS on extracellular serotonin (5-HT) levels in hippocampus, comparing high-chirping (HC) and low-chirping (LC) rats. Methods: Male rats were classified as HC- and LC-rats on the basis of stable levels of USV response using sessions of tickling-like stimulation. CVS procedure lasted 4 weeks. The administration of citalopram (1 mu M) and measurements of levels of 5-HT were done by microdialysis. Corticosterone levels were also measured from trunk blood. Results: Male LC-rats were more sensitive to CVS: the effect of stress on body weight gain was larger and corticosterone levels from full blood were higher in the stressed LC animals as compared to both the unstressed groups and the stressed HC animals. While no baseline differences in extracellular 5-HT levels in hippocampus were found between groups, the increase in extracellular 5-HT levels induced by citalopram was much higher in LC-rats. Conclusion: Chronic stress appears to modify hippocampal 5-HT overflow in rats with low positive affectivity. This finding supports the notion of greater vulnerability to CVS in male rats with low positive affectivity.