Dim Light at Night and Constant Darkness: Two Frequently Used Lighting Conditions That Jeopardize the Health and Well-being of Laboratory Rodents.

The influence of light on mammalian physiology and behavior is due to the entrainment of circadian rhythms complemented with a direct modulation of light that would be unlikely an outcome of circadian system. In mammals, physiological and behavioral circadian rhythms are regulated by the suprachiasmatic nucleus (SCN) of the hypothalamus. This central control allows organisms to predict and anticipate environmental change, as well as to coordinate different rhythmic modalities within an individual. In adult mammals, direct retinal projections to the SCN are responsible for resetting and synchronizing physiological and behavioral rhythms to the light-dark (LD) cycle. Apart from its circadian effects, light also has direct effects on certain biological functions in such a way that the participation of the SCN would not be fundamental for this network. The objective of this review is to increase awareness, within the scientific community and commercial providers, of the fact that laboratory rodents can experience a number of adverse health and welfare outcomes attributed to commonly-used lighting conditions in animal facilities during routine husbandry and scientific procedures, widely considered as "environmentally friendly." There is increasing evidence that exposure to dim light at night, as well as chronic constant darkness, challenges mammalian physiology and behavior resulting in disrupted circadian rhythms, neural death, a depressive-behavioral phenotype, cognitive impairment, and the deregulation of metabolic, physiological, and synaptic plasticity in both the short and long terms. The normal development and good health of laboratory rodents requires cyclical light entrainment, adapted to the solar cycle of day and night, with null light at night and safe illuminating qualities during the day. We therefore recommend increased awareness of the limited information available with regards to lighting conditions, and therefore that lighting protocols must be taken into consideration when designing experiments and duly highlighted in scientific papers. This practice will help to ensure the welfare of laboratory animals and increase the likelihood of producing reliable and reproducible results.

Circadian Forced Desynchrony of the Master Clock Leads to Phenotypic Manifestation of Depression in Rats.

In mammals, a master circadian clock within the suprachiasmatic nucleus (SCN) of the hypothalamus maintains the phase coherence among a wide array of behavioral and physiological circadian rhythms. Affective disorders are typically associated with disruption of this fine-tuned "internal synchronization," but whether this internal misalignment is part of the physiopathology of mood disorders is not clear. To date, depressive-like behavior in animal models has been induced by methods that fail to specifically target the SCN regulation of internal synchronization as the mode to generate depression. In the rat, exposure to a 22-h light-dark cycle (LD22) leads to the uncoupling of two distinct populations of neuronal oscillators within the SCN. This genetically, neurally, and pharmacologically intact animal model represents a unique opportunity to assess the effect of a systematic challenge to the central circadian pacemaker on phenotypic manifestations of mood disorders. We show that LD22 circadian forced desynchrony in rats induces depressive-like phenotypes including anhedonia, sexual dysfunction, and increased immobility in the forced swim test (FST), as well as changes in the levels and turnover rates of monoamines within the prefrontal cortex. Desynchronized rats show increased FST immobility during the dark (active) phase but decreased immobility during the light (rest) phase, suggesting a decrease in the amplitude of the normal daily oscillation in this behavioral manifestation of depression. Our results support the notion that the prolonged internal misalignment of circadian rhythms induced by environmental challenge to the central circadian pacemaker may constitute part of the etiology of depression.

Circadian regulation of arousal: role of the noradrenergic locus coeruleus system and light exposure.

STUDY OBJECTIVES: Noradrenergic locus coeruleus (LC) neurons regulate arousal. Previous studies have shown that noradrenergic LC neurons exhibit a circadian rhythm in impulse activity, which peaks during the active period. This is mediated by an indirect circuit projection from the suprachiasmatic nucleus (SCN) to the LC. Here we sought to evaluate the hypothesis that the LC regulates the circadian properties of the sleep-wake cycle. DESIGN: Sprague-Dawley rats maintained on a light-dark (LD) schedule or in constant darkness (DD) for 3 to 4 weeks were treated with DSP-4, a neurotoxic agent specific for noradrenergic-LC projections. Vigilance states were analyzed before and 3 weeks after LC lesion. The DSP-4 lesion was verified by immunohistochemistry of noradrenergic fibers in the frontal cortex. SETTING: University of Pennsylvania. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: DSP-4 decreased the amplitude of the sleep-wake rhythm in LD animals by significantly decreasing wakefulness and increasing sleep during the active period. However, DSP-4 had no effect on the sleep-wake cycle of DD animals. Moreover, DD itself decreased the amplitude of the sleep-wake cycle similar to that of the neurotoxic lesion of the noradrenergic system in LD animals. Analysis of noradrenergic fiber staining in the frontal cortex revealed that this effect was associated with fewer fibers or boutons in nonlesioned DD rats than in nonlesioned LD animals. CONCLUSIONS: Noradrenergic LC neurons provide a circadian regulation of the sleep-wake cycle, and the maintenance of LC function depends on light exposure. Light deprivation induces a loss of noradrenergic fibers, which in turn decreases the amplitude of the sleep-wake rhythm.