Research reportNeonatal exposure to constant light prevents anhedonia-like behavior induced by constant light exposure in adulthood
Highlights
► Constant light promoted depressive-like behavior, which was reversed by imipramine. ► Neonatal exposure of constant light prevented the constant light-induced anedonia. ► Neonatal exposure to constant darkness facilitated constant light-induced anedonia. ► These data reinforce the relation between mood disorders and circadian rhythms.
Introduction
Disturbances in circadian rhythm have been associated with mood disorders. Changes in mood throughout the day are a common trait in depressed patients [1] and a worse pattern in the morning is incorporated in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision, criteria for the melancholic subtype of major depression [2]. Alterations in circadian rhythms, including the sleep/wake cycle, are heterogeneous in major depressive disorder but generally include high core body temperature at night, early cortisol secretion, reduced slow wave sleep, and increased and phase-advanced rapid eye movement sleep (reviewed in [3]). Core body temperature may even lack 24 h rhythmicity in some depressed patients [4]. Patients may show internal desynchronization or can be considered free-running [5], [6], [7].
In humans, depression is also associated with a reduction of light during the winter. Seasonal affective disorder occurs more frequently in countries located in high latitudes [8]. Most patients have phase delays in their circadian rhythm, but a small subgroup is phase-advanced in winter depression [9]. Accordingly, diurnal rats kept under short photoperiods or that received melatonin injections during the light phase of the light/dark cycle show depressive-like behavior in the forced swim and sucrose preference tests [10], [11]. Exposure to 1 h of bright light was shown to reverse depressive-like behavior in the forced swim test [12]. Not only diurnal rodents were shown to be affected by short periods, but also nocturnal animals, such as the Siberian hamsters [13], [14] and Wistar rats [15]. It was also observed in Wistar rats that total light deprivation for 6 weeks promotes depressive-like behavior in the forced swim test in adulthood and damages monoaminergic neurons [16].
By contrast, mice exposed for 3 weeks to constant light exhibited depressive-like behavior in the sucrose preference and forced swim tests, which was partially prevented by enriching the environment with an opaque tube that allowed the mice to escape from the light [17]. Prolonged exposure to constant light is also known to promote arrhythmicity of locomotor activity [18]. However, neonatal exposure to constant illumination was reported to prevent the loss of rhythmicity of locomotor activity in rats [19], [20].
Thus, the main objective of the present study was to investigate whether neonatal constant light exposure prevents anhedonia-like behavior induced by constant illumination in adulthood.
Section snippets
Animals and study design
Adult male and female Wistar rats were obtained from the Federal University of Paraná and kept under controlled temperature (22 ± 3 °C) and a 12 h/12 h light/dark (LD) cycle (lights on 07:00–19:00 h). Food and water were available ad libitum. All animal procedures were approved by the Ethical Committee of Animal Experiment (protocol no. 389) and in accordance with the Guide for the Care and Use of Laboratory Animals adopted by the Department of Pharmacology, Federal University of Paraná.
In experiment
LL in adulthood induces anhedonia and it is prevented by neonatal exposure to LL
In experiment 1, after 3 weeks of constant illumination, the LL group exhibited a reduction in sucrose preference compared with the LD group (U = 79, p < 0.05) and its own baseline (T = 29, p < 0.05, Fig. 1). The data were further replicated in the fourth week of constant light (U = 96, p < 0.05; T = 4, p < 0.05). Imipramine treatment reversed LL-induced anhedonia-like behavior (Fig. 2). In the LL group, imipramine-treated animals had higher sucrose preference compared with LL controls (U = 9, p < 0.05).
In
Discussion
In accordance to our initial hypothesis, animals exposed to constant light during lactation did not reduced sucrose preference when submitted to three weeks of constant light exposure in adulthood. As described previously for mice [17], we found that constant light induces depressive-like behavior in adulthood of neonatally naïve rats. Moreover, to our knowledge, we showed for the first time that imipramine treatment can reverse anhedonia-like behavior in this animal model. We also found that
Conclusion
In conclusion, our data corroborate the evidence and hypothesis regarding an important role of circadian rhythm disruption and neonatal stress in the development of mood disorders. In addition to already existing chronobiological therapeutics for depression, such as one night of sleep deprivation and bright light in the morning [35], we propose that the prevention of circadian rhythm disturbances may lower the risk of developing major depressive disorder.
Acknowledgments
D.C. and B.J.M. are recipients of student graduate fellowships from CAPES; L.H.M. is recipient of a student undergraduate fellowship from CNPq; M.L.A., F.M.L. and R.A. are recipients of research fellowships from CNPq.
References (35)
- et al.
A longitudinal study of diurnal mood variation in depression: characteristics and significance
J Affect Disord
(1994) - et al.
The circadian basis of mood disorders: recent developments and treatment implications
Eur Neuropsychopharmacol
(2008) - et al.
Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression
Eur Neuropsychopharmacol
(2001) - et al.
Uncoupling of social zeitgebers and diurnal cortisol secretion in clinical depression
Psychoneuroendocrinology
(2004) - et al.
Seasonal affective disorder and latitude: a review of the literature
J Affect Disord
(1999) - et al.
Sand rats see the light: short photoperiod induces a depression-like response in a diurnal rodent
Behav Brain Res
(2006) - et al.
Effects of bright light treatment on depression- and anxiety-like behaviors of diurnal rodents maintained on a short daylight schedule
Behav Brain Res
(2009) - et al.
Affective responses to changes in day length in Siberian hamsters (Phodopus sungorus)
Psychoneuroendocrinology
(2005) - et al.
Influence of light at night on murine anxiety- and depressive-like responses
Behav Brain Res
(2009) - et al.
Constant bright light (LL) during lactation in rats prevents arrhythmicity due to LL
Physiol Behav
(1998)
Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood
Biol Psychiatry
Attenuation of high sweet solution preference by mood stabilizers: a possible mouse model for the increased reward-seeking domain of mania
J Neurosci Methods
Magnesium sulfate and sodium valproate block methylphenidate-induced hyperlocomotion, an animal model of mania
Pharmacol Rep
Susceptibility of a potential animal model for pathological anxiety to chronic mild stress
Behav Brain Res
Repeated paroxetine treatment reverses anhedonia induced in rats by chronic mild stress or dexamethasone
Eur Neuropsychopharmacol
Exposure of mice to long-light: a new animal model to study depression
Eur Neuropsychopharmacol
Quantitative changes in neuronal and glial cells in the suprachiasmatic nucleus as a function of the lighting conditions during weaning
Brain Res Dev Brain Res
Cited by (22)
Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson's disease
2021, Brain Research BulletinCitation Excerpt :The amount of fluid consumed was calculated by the initial weight minus the final weight of the bottles 24 h later. The sum of water consumption and sucrose consumption was defined as the total intake, and the preference was calculated as the percentage of the volume of sucrose intake over the total volume of fluid intake (Martynhak et al., 2011). Before surgery, the basal test was performed to select rats with a preference for sucrose, and the animals with less than 70 % sucrose preference were excluded from the study.
The role of sleep disturbances in depressive-like behavior with emphasis on α-ketoglutarate dehydrogenase activity in rats.
2020, Physiology and BehaviorCitation Excerpt :Therefore, we mention to the role of circadian rhythm. It has been revealed that any disruption in the cycle of the circadian rhythm is associated with mood disorders including depression [39, 40]. Disruption in the circadian molecular mechanism is related to the depression [41].
Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like behavior in 6-OHDA lesioned rats
2018, Physiology and BehaviorEffects of light exposure at night during development
2016, Current Opinion in Behavioral SciencesSocial interaction with rat exposed to constant light during lactation prevents depressive-like behavior induced by constant light in adulthood
2015, Neuroscience LettersCitation Excerpt :All of the animal procedures were approved by the Ethical Committee of Animal Experimentation of the Federal University of Paraná (protocol no. 600) and were in accordance with the Guide for the Care and Use of Laboratory Animals adopted by the Department of Pharmacology, Federal University of Paraná. The mating procedure involved placing each male in a cage with three female rats for 1 week as described previously [19]. For this experiment, 18 females were used, and 13 of them had litters.