Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3-/- mice, but not wildtype mice

Sci Rep. 2017 Jan 10:7:40399. doi: 10.1038/srep40399.

Abstract

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3-/- mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3-/-) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3-/- mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3-/- nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3-/- phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light.

MeSH terms

  • Anhedonia / drug effects
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Circadian Rhythm / physiology
  • Gene Expression Regulation / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Humans
  • Imipramine / administration & dosage
  • Mice
  • Mice, Knockout
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Period Circadian Proteins / genetics*
  • Photoperiod
  • Sleep / genetics
  • Sleep / physiology
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / genetics
  • Sleep Wake Disorders / physiopathology

Substances

  • Brain-Derived Neurotrophic Factor
  • Per3 protein, mouse
  • Period Circadian Proteins
  • Imipramine