title: Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats.
abstract: Light is an important environmental factor for regulation of mood. There is a high frequency of seasonal affective disorder in high latitudes where light exposure is limited, and bright light therapy is a successful antidepressant treatment. We recently showed that rats kept for 6 weeks in constant darkness (DD) have anatomical and behavioral features similar to depressed patients, including dysregulation of circadian sleep-waking rhythms and impairment of the noradrenergic (NA)-locus coeruleus (LC) system. Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergic-ventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats. We found increased apoptosis in the three aminergic systems analyzed when compared with animals maintained for 6 weeks in 12:12 light-dark conditions. The most apoptosis was observed in NA-LC neurons, associated with a significant decrease in the number of cortical NA boutons. Behaviorally, DD induced a depression-like condition as measured by increased immobility in a forced swim test (FST). DD did not appear to be stressful (no effect on adrenal or body weights) but may have sensitized responses to subsequent stressors (increased fecal number during the FST). We also found that the antidepressant desipramine decreases these neural and behavioral effects of light deprivation. These findings indicate that DD induces neural damage in monoamine brain systems and this damage is associated with a depressive behavioral phenotype. Our results suggest a mechanism whereby prolonged limited light intensity could negatively impact mood.
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6100, USA.
authors.forename: M M C
authors.initials: MM
authors.lastname: Gonzalez
authors.forename: G
authors.initials: G
authors.lastname: Aston-Jones
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001679:Biogenic Amines / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003624:Darkness; D003863:Depression / Q000503:physiopathology*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010641:Phenotype; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects / Q000473:pathology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000473:pathology
chemical_list: D001679:Biogenic Amines; D012701:Serotonin; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine