Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod

Abstract

Seasonal affective disorder (SAD), beyond mood changes, is characterized by alterations in daily rhythms of behavior and physiology. The pathophysiological conditions of SAD involve changes in day length and its first-line treatment is bright light therapy. Animal models using nocturnal rodents have been studied to elucidate the neurobiological mechanisms of depression, but might be ill suited to study the therapeutic effects of light in SAD since they exhibit light-aversive responses. Here Arvicanthis ansorgei, a diurnal rodent, was used to determine behavioral, molecular and brain dopamine changes in response to exposure to a winter-like photoperiod consisting of a light–dark cycle with 8 h of light, under diminished light intensity, and 16 h of darkness. Furthermore, we evaluated whether timed-daily bright light exposure has an effect on behavior and brain physiology of winter-like exposed animals. Arvicanthis under a winter-like condition showed alterations in the synchronization of the locomotor activity rhythm to the light–dark cycle. Moreover, alterations in day–night activity of dopaminergic neurotransmission were revealed in the nucleus accumbens and the dorsal striatum, and in the day–night clock gene expression in the suprachiasmatic nucleus. Interestingly, whereas dopamine disturbances were reversed in animals exposed to daily light at early or late day, altered phase of the daily rhythm of locomotion was reverted only in animals exposed to light at the late day. Moreover, Per2 gene expression in the SCN was also affected by light exposure at late day in winter-like exposed animals. These findings suggest that light induces effects on behavior by mechanisms that rely on both circadian and rhythm-independent pathways influencing the dopaminergic circuitry. This last point might be crucial for understanding the mechanisms of non-pharmacological treatment in SAD.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Abilio VC, Freitas FM, Dolnikoff MS, Castrucci AM, Frussa-Filho R (1999) Effects of continuous exposure to light on behavioral dopaminergic supersensitivity. Biol Psychiatry 45(12):1622–1629

  2. Adidharma W, Leach G, Yan L (2012) Orexinergic signaling mediates light-induced neuronal activation in the dorsal raphe nucleus. Neuroscience 220:201–207. https://doi.org/10.1016/j.neuroscience.2012.06.020

  3. Albrecht U (2017) Molecular mechanisms in mood regulation involving the Circadian Clock. Front Neurol 8:30. https://doi.org/10.3389/fneur.2017.00030

  4. Ashkenazy-Frolinger T, Kronfeld-Schor N, Juetten J, Einat H (2010) It is darkness and not light: Depression-like behaviors of diurnal unstriped Nile grass rats maintained under a short photoperiod schedule. J Neurosci Methods 186(2):165–170. https://doi.org/10.1016/j.jneumeth.2009.11.013

  5. Bagchi SP (1998) Striatal and urinary DOPAC/DA ratio may indicate a long-lasting DA release enhancement by MPP + and MPTP. Neurochem Res 23(2):127–134

  6. Baker PM, Mizumori SJY (2017) Control of behavioral flexibility by the lateral habenula. Pharmacol Biochem Behav. https://doi.org/10.1016/j.pbb.2017.07.012

  7. Berman K, Lam RW, Goldner EM (1993) Eating attitudes in seasonal affective disorder and bulimia nervosa. J Affect Disord 29(4):219–225

  8. Berridge KC, Kringelbach ML (2013) Neuroscience of affect: brain mechanisms of pleasure and displeasure. Curr Opin Neurobiol 23(3):294–303. https://doi.org/10.1016/j.conb.2013.01.017

  9. Brene S, Bjornebekk A, Aberg E, Mathe AA, Olson L, Werme M (2007) Running is rewarding and antidepressive. Physiol Behav 92(1–2):136–140. https://doi.org/10.1016/j.physbeh.2007.05.015

  10. Burgess HJ, Fogg LF, Young MA, Eastman CI (2004) Bright light therapy for winter depression—Is phase advancing beneficial? Chronobiol Int 21(4–5):759–775

  11. Caldelas I, Poirel VJ, Sicard B, Pevet P, Challet E (2003) Circadian profile and photic regulation of clock genes in the suprachiasmatic nucleus of a diurnal mammal Arvicanthis ansorgei. Neuroscience 116(2):583–591

  12. Cawley EI, Park S, aan het Rot M, Sancton K, Benkelfat C, Young SN, Boivin DB, Leyton M (2013) Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder. J Psychiatry Neurosci 38(6):388–397. https://doi.org/10.1503/jpn.120181

  13. Dahl K, Avery DH, Lewy AJ, Savage MV, Brengelmann GL, Larsen LH, Vitiello MV, Prinz PN (1993) Dim light melatonin onset and circadian temperature during a constant routine in hypersomnic winter depression. Acta Psychiatr Scand 88(1):60–66

  14. Deats SP, Adidharma W, Yan L (2015) Hypothalamic dopaminergic neurons in an animal model of seasonal affective disorder. Neurosci Lett 602:17–21. https://doi.org/10.1016/j.neulet.2015.06.038

  15. Deibel SH, Hong NS, Himmler SM, McDonald RJ (2014) The effects of chronic photoperiod shifting on the physiology of female Long-Evans rats. Brain Res Bull 103:72–81. https://doi.org/10.1016/j.brainresbull.2014.03.001

  16. Diehl DJ, Mintun MA, Kupfer DJ, Moore RY (1994) A likely in vivo probe of human circadian timing system function using PET. Biol Psychiatry 36(8):562–565

  17. Dremencov E, El Mansari M, Blier P (2009) Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area. J Psychiatry Neurosci 34(3):223–229

  18. Eisenberg DP, Kohn PD, Baller EB, Bronstein JA, Masdeu JC, Berman KF (2010) Seasonal effects on human striatal presynaptic dopamine synthesis. J Neurosci 30(44):14691–14694. https://doi.org/10.1523/JNEUROSCI.1953-10.2010

  19. Gonzalez MM, Aston-Jones G (2008) Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats. Proc Natl Acad Sci USA 105(12):4898–4903. https://doi.org/10.1073/pnas.0703615105

  20. Grippo RM, Purohit AM, Zhang Q, Zweifel LS, Guler AD (2017) Direct midbrain dopamine input to the suprachiasmatic nucleus accelerates circadian entrainment. Curr Biol. https://doi.org/10.1016/j.cub.2017.06.084

  21. Hampp G, Ripperger JA, Houben T, Schmutz I, Blex C, Perreau-Lenz S, Brunk I, Spanagel R, Ahnert-Hilger G, Meijer JH, Albrecht U (2008) Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr Biol 18(9):678–683. https://doi.org/10.1016/j.cub.2008.04.012

  22. Hartikainen P, Soininen H, Reinikainen KJ, Sirvio J, Soikkeli R, Riekkinen PJ (1991) Neurotransmitter markers in the cerebrospinal fluid of normal subjects. Effects of aging and other confounding factors. J Neural Transm Gen Sect 84(1–2):103–117

  23. Hattar S, Kumar M, Park A, Tong P, Tung J, Yau KW, Berson DM (2006) Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol 497(3):326–349. https://doi.org/10.1002/cne.20970

  24. Hood S, Cassidy P, Cossette MP, Weigl Y, Verwey M, Robinson B, Stewart J, Amir S (2010) Endogenous dopamine regulates the rhythm of expression of the clock protein PER2 in the rat dorsal striatum via daily activation of D2 dopamine receptors. J Neurosci 30(42):14046–14058. https://doi.org/10.1523/JNEUROSCI.2128-10.2010

  25. Krivisky K, Ashkenazy T, Kronfeld-Schor N, Einat H (2011) Antidepressants reverse short-photoperiod-induced, forced swim test depression-like behavior in the diurnal fat sand rat: further support for the utilization of diurnal rodents for modeling affective disorders. Neuropsychobiology 63(3):191–196. https://doi.org/10.1159/000321805

  26. Lam RW, Levitan RD (2000) Pathophysiology of seasonal affective disorder: a review. J Psychiatry Neurosci 25(5):469–480

  27. Lazzerini Ospri L, Prusky G, Hattar S (2017) Mood, the circadian system, and melanopsin retinal ganglion cells. Annu Rev Neurosci 40:539–556. https://doi.org/10.1146/annurev-neuro-072116-031324

  28. Leach G, Adidharma W, Yan L (2013a) Depression-like responses induced by daytime light deficiency in the diurnal grass rat (Arvicanthis niloticus). PLoS One 8(2):e57115. https://doi.org/10.1371/journal.pone.0057115

  29. Leach G, Ramanathan C, Langel J, Yan L (2013b) Responses of brain and behavior to changing day-length in the diurnal grass rat (Arvicanthis niloticus). Neuroscience 234:31–39. https://doi.org/10.1016/j.neuroscience.2013.01.002

  30. LeGates TA, Fernandez DC, Hattar S (2014) Light as a central modulator of circadian rhythms, sleep and affect. Nat Rev Neurosci 15(7):443–454. https://doi.org/10.1038/nrn3743

  31. Lewy AJ, Bauer VK, Cutler NL, Sack RL, Ahmed S, Thomas KH, Blood ML, Jackson JM (1998) Morning vs evening light treatment of patients with winter depression. Arch Gen Psychiatry 55(10):890–896

  32. Lewy AJ, Lefler BJ, Emens JS, Bauer VK (2006) The circadian basis of winter depression. Proc Natl Acad Sci USA 103(19):7414–7419. https://doi.org/10.1073/pnas.0602425103

  33. Lieverse R, Van Someren EJ, Nielen MM, Uitdehaag BM, Smit JH, Hoogendijk WJ (2011) Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry 68(1):61–70. https://doi.org/10.1001/archgenpsychiatry.2010.183

  34. Logan RW, Edgar N, Gillman AG, Hoffman D, Zhu X, McClung CA (2015) Chronic stress induces brain region-specific alterations of molecular rhythms that correlate with depression-like behavior in mice. Biol Psychiatry 78(4):249–258. https://doi.org/10.1016/j.biopsych.2015.01.011

  35. Luo AH, Aston-Jones G (2009) Circuit projection from suprachiasmatic nucleus to ventral tegmental area: a novel circadian output pathway. Eur J Neurosci 29(4):748–760. https://doi.org/10.1111/j.1460-9568.2008.06606.x

  36. McCune AM, Lundgren JD (2015) Bright light therapy for the treatment of night eating syndrome: A pilot study. Psychiatry Res 229(1–2):577–579. https://doi.org/10.1016/j.psychres.2015.07.079

  37. Mendoza J (2017) Circadian neurons in the lateral habenula: clocking motivated behaviors. Pharmacol Biochem Behav. https://doi.org/10.1016/j.pbb.2017.06.013

  38. Mendoza J, Challet E (2014) Circadian insights into dopamine mechanisms. Neuroscience 282:230–242. https://doi.org/10.1016/j.neuroscience.2014.07.081

  39. Mendoza J, Gourmelen S, Dumont S, Sage-Ciocca D, Pevet P, Challet E (2012) Setting the main circadian clock of a diurnal mammal by hypocaloric feeding. J Physiol 590(13):3155–3168. https://doi.org/10.1113/jphysiol.2012.230300

  40. Moga MM, Weis RP, Moore RY (1995) Efferent projections of the paraventricular thalamic nucleus in the rat. J Comp Neurol 359(2):221–238. https://doi.org/10.1002/cne.903590204

  41. Moorman DE, Aston-Jones G (2010) Orexin/hypocretin modulates response of ventral tegmental dopamine neurons to prefrontal activation: diurnal influences. J Neurosci 30(46):15585–15599. https://doi.org/10.1523/JNEUROSCI.2871-10.2010

  42. Neumeister A, Konstantinidis A, Praschak-Rieder N, Willeit M, Hilger E, Stastny J, Kasper S (2001) Monoaminergic function in the pathogenesis of seasonal affective disorder. Int J Neuropsychopharmacol 4(4):409–420. https://doi.org/10.1017/S1461145701002644

  43. Opmeer EM, Kortekaas R, Aleman A (2010) Depression and the role of genes involved in dopamine metabolism and signalling. Prog Neurobiol 92(2):112–133. https://doi.org/10.1016/j.pneurobio.2010.06.003

  44. Partonen T, Treutlein J, Alpman A, Frank J, Johansson C, Depner M, Aron L, Rietschel M, Wellek S, Soronen P, Paunio T, Koch A, Chen P, Lathrop M, Adolfsson R, Persson ML, Kasper S, Schalling M, Peltonen L, Schumann G (2007) Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression. Ann Med 39(3):229–238. https://doi.org/10.1080/07853890701278795

  45. Pinchasov BB, Shurgaja AM, Grischin OV, Putilov AA (2000) Mood and energy regulation in seasonal and non-seasonal depression before and after midday treatment with physical exercise or bright light. Psychiatry Res 94(1):29–42

  46. Raoux N, Benoit O, Dantchev N, Denise P, Franc B, Allilaire JF, Widlocher D (1994) Circadian pattern of motor activity in major depressed patients undergoing antidepressant therapy: relationship between actigraphic measures and clinical course. Psychiatry Res 52(1):85–98

  47. Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Davenport Y, Mueller PS, Newsome DA, Wehr TA (1984) Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 41(1):72–80

  48. Ruger M, St Hilaire MA, Brainard GC, Khalsa SB, Kronauer RE, Czeisler CA, Lockley SW (2013) Human phase response curve to a single 6.5 h pulse of short-wavelength light. J Physiol 591(1):353–363. https://doi.org/10.1113/jphysiol.2012.239046

  49. Russo SJ, Nestler EJ (2013) The brain reward circuitry in mood disorders. Nat Rev Neurosci 14(9):609–625. https://doi.org/10.1038/nrn3381

  50. Salaberry NL, Mendoza J (2015) Insights into the role of the habenular circadian clock in addiction. Front Psychiatry 6:179. https://doi.org/10.3389/fpsyt.2015.00179

  51. Shuboni DD, Cramm S, Yan L, Nunez AA, Smale L (2012) Acute behavioral responses to light and darkness in nocturnal Mus musculus and diurnal Arvicanthis niloticus. J Biol Rhythms 27(4):299–307. https://doi.org/10.1177/0748730412449723

  52. Shuboni DD, Cramm SL, Yan L, Ramanathan C, Cavanaugh BL, Nunez AA, Smale L (2015) Acute effects of light on the brain and behavior of diurnal Arvicanthis niloticus and nocturnal Mus musculus. Physiol Behav 138:75–86. https://doi.org/10.1016/j.physbeh.2014.09.006

  53. St Hilaire MA, Gooley JJ, Khalsa SB, Kronauer RE, Czeisler CA, Lockley SW (2012) Human phase response curve to a 1 h pulse of bright white light. J Physiol 590(13):3035–3045. https://doi.org/10.1113/jphysiol.2012.227892

  54. Stahl SM, Lee-Zimmerman C, Cartwright S, Morrissette DA (2013) Serotonergic drugs for depression and beyond. Curr Drug Targets 14(5):578–585

  55. Tavolaro FM, Thomson LM, Ross AW, Morgan PJ, Helfer G (2015) Photoperiodic effects on seasonal physiology, reproductive status and hypothalamic gene expression in young male F344 rats. J Neuroendocrinol 27(2):79–87. https://doi.org/10.1111/jne.12241

  56. Teicher MH, Glod CA, Magnus E, Harper D, Benson G, Krueger K, McGreenery CE (1997) Circadian rest-activity disturbances in seasonal affective disorder. Arch Gen Psychiatry 54(2):124–130

  57. Terman M, Terman JS (2005) Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects. CNS Spectr 10(8):647–663 (quiz 672)

  58. Terman M, Terman JS, Quitkin FM, Cooper TB, Lo ES, Gorman JM, Stewart JW, McGrath PJ (1988) Response of the melatonin cycle to phototherapy for seasonal affective disorder. Short note. J Neural Transm 72(2):147–165

  59. Tsai HY, Chen KC, Yang YK, Chen PS, Yeh TL, Chiu NT, Lee IH (2011) Sunshine-exposure variation of human striatal dopamine D(2)/D(3) receptor availability in healthy volunteers. Prog Neuropsychopharmacol Biol Psychiatry 35(1):107–110. https://doi.org/10.1016/j.pnpbp.2010.09.014

  60. Verwey M, Dhir S, Amir S (2016) Circadian influences on dopamine circuits of the brain: regulation of striatal rhythms of clock gene expression and implications for psychopathology and disease. F1000Res. https://doi.org/10.12688/f1000research.9180.1

  61. Volkers AC, Tulen JH, Van Den Broek WW, Bruijn JA, Passchier J, Pepplinkhuizen L (2002) 24-Hour motor activity after treatment with imipramine or fluvoxamine in major depressive disorder. Eur Neuropsychopharmacol 12(4):273–278

  62. Willeit M, Sitte HH, Thierry N, Michalek K, Praschak-Rieder N, Zill P, Winkler D, Brannath W, Fischer MB, Bondy B, Kasper S, Singer EA (2008) Enhanced serotonin transporter function during depression in seasonal affective disorder. Neuropsychopharmacology 33(7):1503–1513. https://doi.org/10.1038/sj.npp.1301560

  63. Wirz-Justice A, Graw P, Krauchi K, Gisin B, Jochum A, Arendt J, Fisch HU, Buddeberg C, Poldinger W (1993) Light therapy in seasonal affective disorder is independent of time of day or circadian phase. Arch Gen Psychiatry 50(12):929–937

Download references

Acknowledgements

We thank Dr. Dominique Ciocca for help with Arvicanthis breeding. Funding sources of the present study were provided by the Agence National de la Recherche (ANR-14-CE13-0002-01 ADDiCLOCK JCJC to JM), the Centre National de la Recherche Scientifique (JM), and the Institut Danone France-Fondation pour la Recherche Médicale Consortium (JM). JI is a Ph.D. NeuroTime program fellow, an Erasmus Mundus program funded by the European Commission (NeuroTime Grant: 520124-1-2011-1-FR-ERA). Riboprobe used for Per2 gene detection was generously provided by Prof. Hitoshi Okamura (Kyoto University, Japan). We thank Dr. Hughes Dardente (University of Tours, France) for the Avp and Bmal1 clones.

Author information

Correspondence to Jorge Mendoza.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Pub. No. 86-23, revised 1985) and the French Department of Agriculture (License no. 67-378 to J.M.).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Itzhacki, J., Clesse, D., Goumon, Y. et al. Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod. Brain Struct Funct 223, 2641–2652 (2018). https://doi.org/10.1007/s00429-018-1655-8

Download citation

Keywords

  • Circadian
  • Dopamine
  • Light
  • Striatum
  • Reward
  • Mood
  • Clock genes
  • Arvicanthis