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Circadian genes P eriod 1 and P eriod 2 in the nucleus accumbens regulate anxiety‐related behavior
Author(s) -
Spencer Sade,
Falcon Edgardo,
Kumar Jaswinder,
Krishnan Vaishnav,
Mukherjee Shibani,
Birnbaum Shari G.,
McClung Colleen A.
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12010
Subject(s) - nucleus accumbens , gene knockdown , circadian rhythm , anxiety , endocrinology , medicine , psychology , amygdala , extended amygdala , gene , biology , psychiatry , genetics , dopamine
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 mP eriod 1 ( mP er1 ) or mP eriod 2 ( mP er2 ) individually did not have consistent behavioral abnormalities in measures of anxiety‐related behavior. However, mice deficient in both mP er1 and mP er2 had an increase in levels of anxiety‐like behavior in multiple measures. Moreover, we found that mP er1 and mP er2 expression was reduced in the nucleus accumbens ( NA c) after exposure to chronic social defeat stress, a paradigm that led to increased anxiety‐related behavior. Following social defeat, chronic treatment with fluoxetine normalized P er gene expression towards wild‐type levels. Knockdown of both mP er1 and mP er2 expression via RNA interference specifically in the NA c led to a similar increase in anxiety‐like behavior as seen in the mutant animals. Taken together, these results implicate the P er genes in the NA c in response to stress and the development of anxiety.