title: Circadian genes Period 1 and Period 2 in the nucleus accumbens regulate anxiety-related behavior.
abstract: It has been suggested for some time that circadian rhythm abnormalities underlie the development of multiple psychiatric disorders. However, it is unclear how disruptions in individual circadian genes might regulate mood and anxiety. Here we found that mice lacking functional mPeriod 1 (mPer1) or mPeriod 2 (mPer2) individually did not have consistent behavioral abnormalities in measures of anxiety-related behavior. However, mice deficient in both mPer1 and mPer2 had an increase in levels of anxiety-like behavior in multiple measures. Moreover, we found that mPer1 and mPer2 expression was reduced in the nucleus accumbens (NAc) after exposure to chronic social defeat stress, a paradigm that led to increased anxiety-related behavior. Following social defeat, chronic treatment with fluoxetine normalized Per gene expression towards wild-type levels. Knockdown of both mPer1 and mPer2 expression via RNA interference specifically in the NAc led to a similar increase in anxiety-like behavior as seen in the mutant animals. Taken together, these results implicate the Per genes in the NAc in response to stress and the development of anxiety.
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA. mcclungca@upmc.edu
authors.forename: Sade
authors.initials: S
authors.lastname: Spencer
authors.forename: Edgardo
authors.initials: E
authors.lastname: Falcon
authors.forename: Jaswinder
authors.initials: J
authors.lastname: Kumar
authors.forename: Vaishnav
authors.initials: V
authors.lastname: Krishnan
authors.forename: Shibani
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Shari G
authors.initials: SG
authors.lastname: Birnbaum
authors.forename: Colleen A
authors.initials: CA
authors.lastname: McClung
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D001362:Avoidance Learning; D005473:Fluoxetine / Q000494:pharmacology; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000502:physiology; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D013315:Stress, Psychological; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018687:Antidepressive Agents, Second-Generation; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D034741:RNA, Small Interfering; D005473:Fluoxetine