Abstract

Disrupted circadian rhythms are a core feature of mood and anxiety disorders. Circadian rhythms are coordinated by a light-entrainable master clock located in the suprachiasmatic nucleus. Animal models of mood and anxiety disorders often exhibit blunted rhythms in locomotor activity and clock gene expression. Interestingly, the changes in circadian rhythms correlate with mood-related behaviours. Although animal models of depression and anxiety exhibit aberrant circadian rhythms in physiology and behavior, it is possible that the methodology being used to induce the behavioral phenotype (e.g., brain lesions, chronic stress, global gene deletion) affect behavior independently of circadian system. This study investigates the relationship between individual differences in circadian locomotor parameters and mood-related behaviors in healthy rats. The circadian phenotype of male Lewis rats was characterized by analyzing wheel running behavior under 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, restricted feeding, elevated plus maze, forced swim test, and fear conditioning. Under 12h:12h LD conditions, percent of daily activity in the light phase and variability in activity onset were associated with longer latency to immobility in the forced swim test. Variability in onset also correlated positively with anxiety-like behavior in the elevated plus maze. Rate of re-entrainment correlated positively with measures of anxiety in the activity box and elevated plus maze. Lastly, we found that free running period under constant dark was associated with anxiety-like behaviors in the activity box and elevated plus maze. Our results provide a previously uncharacterized relationship between circadian locomotor parameters and mood-related behaviors in healthy rats and provide a basis for future examination into circadian clock functioning and mood.

Highlights

  • Disrupted circadian rhythms in physiology and behavior are a core feature of many psychiatric conditions including mood and anxiety disorders [1, 2]

  • Disrupted circadian rhythms in physiology and behavior are a core feature of mood and anxiety disorders [1, 2]

  • In the present study we investigated individual differences in circadian locomotor activity and how they relate to depression- and anxiety-like behaviors in a healthy population of inbred Lewis rats

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Summary

Introduction

Disrupted circadian rhythms in physiology and behavior are a core feature of many psychiatric conditions including mood and anxiety disorders [1, 2]. Circadian locomotor parameters correlate with anxiety- and depression-like behavior insomnia, hypersomnia) are observed in various psychiatric conditions [3]. Concurrent to these changes in sleep/wake rhythms, circadian alterations in daily body temperature rhythms, daily activity patterns, and hormone release have been reported [4, 5]. Several studies have found links between single nucleotide polymorphisms in core clock genes and mood disorders and schizophrenia [8,9,10,11,12] These findings point to some fundamental circadian mechanism acting at the core of certain affective disorders

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