Revealing a Latent Variable: Individual Differences in Affective Response to Repeated Injections

Latent variables may exist in experimental designs and may interfere with reproducibility of findings. The present study reveals 1 such variable, the individual differences in affective response to chronic injection stress, by using the novelty-seeking phenotype as a model of differential emotional reactivity. The phenotype is identified by exposing a population of experimentally naive outbred rats to the mild stress of a novel environment and classifying them as high responders (HR; upper 1/3) and low responders (LR; lower 1/3) based on their locomotor reactivity. Research has shown that HR/LR animals differ in their basal levels of anxiety-and depressive-like behavior, as well as in their response to environmental and pharmacological challenges; suggesting validity of this model in studying individual differences in stress reactivity. The present data showed that 14 daily, intraperitoneal saline injections did not alter the phenotypic differences in social behavior observed basally in HR/LR rats. However, injections significantly increased time spent immobile in the forced swim test in HRs, while the identical regimen significantly decreased the same measure in LRs, compared with handled-controls. These data indicate that individual differences in stress reactivity can have a significant impact on the depressive-like responses to repeated intraperitoneal injections in rats. Given that such underlying emotional variability exists within standard, outbred rat populations, this study highlights the importance of accounting for such variability in any study investigating the effects of repeated drug administration on depressive-like behavior for reliability and replicability of findings. Thus, we recommend including an uninjected control group in all studies.