RT Journal Article
SR Electronic
T1 Circadian Forced Desynchrony of the Master Clock Leads to Phenotypic Manifestation of Depression in Rats
JF eneuro
JO eneuro
FD Society for Neuroscience
SP ENEURO.0237-16.2016
DO 10.1523/ENEURO.0237-16.2016
A1 Miriam Ben-Hamo
A1 Tracy Larson
A1 Leanne S. Duge
A1 Carl Sikkema
A1 Charles W. Wilkinson
A1 Horacio O. de la Iglesia
A1 Mónica M. C. González
YR 2016
UL http://www.eneuro.org/content/early/2016/12/05/ENEURO.0237-16.2016.abstract
AB 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 22h 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.Significance Statement Previous studies hypothesized that disruption of the internal coordination of circadian rhythms by the master circadian clock may contribute to the etiology of mood disorders. This hypothesis has not yet been tested in genetically and neurologically intact animal models with impairment of the master clock’s ability to maintain circadian internal synchronization. We compared rats exposed to 22h light-dark (LD) cycle, which leads to forced desynchrony of neuronal oscillators within the suprachiasmatic nucleus, to rats exposed to a normal 24h LD cycle. We show that forced desynchrony induces a depressive phenotype that is particularly manifested during the dark (active) phase of the animals. Our results demonstrate that prolonged internal misalignment of circadian rhythms may constitute part of the etiology of depression.