Abstract

Disrupted circadian rhythms are a core feature of various psychiatric disorders, including, but not limited to depression and anxiety. At this point, it remains uncertain whether disrupted circadian rhythms are implicated in the pathophysiology of mental disorders or whether the disrupted circadian rhythms are simply a byproduct of the disorder. The objective of this thesis is to explore the relationship between circadian rhythms and mood. The first study examines individual differences in circadian locomotor behavior and mood-related behaviors in rats. The circadian phenotype of male Lewis rats was characterized by analyzing daily wheel running activity under multiple lighting conditions: standard 12h:12h LD conditions, constant dark, constant light, and rate of re-entrainment to a phase advance. Rats were then tested on a battery of behavioral tests: activity box, elevated plus maze (EPM), forced swim test (FST), and fear conditioning.

We found an interesting relationship between entrainment parameters and mood-related behaviors. Under 12h:12h LD conditions, percent of daily activity in the light phase and variability in activity onset were associated with latency to immobility in the FST. Variability in onset was also associated with anxiety-like behavior in the EPM. Rate of re-entrainment correlated with anxiety-like behaviors in the activity box and EPM. Our findings suggest that Lewis rats may be a suitable strain for studying the relationship between circadian rhythms and mood-related behaviors in rodents.

In human clinical populations, comorbidity rates between depression and anxiety are very high. Surprisingly, little attention has been given to the question of comorbidity in animal models. To further examine the utility of Lewis rats for the study of mood-related behaviors we then assessed for comorbidity between depression- and anxiety-like behaviors. Interestingly, our findings indicate suggest that Lewis rats do not exhibit comorbid depression- and anxiety-like behaviors. While the absence of a comorbid relationship between depression- and anxiety-like behaviors may come as a surprise, we present an alternative interpretation of escape-directed behaviors in the FST.