Elevated aggressive behavior in male mice with thyroid-specific Prkar1a and
global Epac1 gene deletion.
Authors Russart KLG, Huk D, Nelson RJ, Kirschner LS
Submitted By Submitted Externally on 1/25/2018
Status Published
Journal Hormones and behavior
Year 2018
Date Published 1/1/2018
Volume : Pages 98 : 121 - 129
PubMed Reference 29289659
Abstract Alterations in circulating thyroid hormone concentrations are associated with
several psychological and behavioral disorders. In humans, behavioral disorders
such as anxiety, depression, and attention-deficit hyperactivity disorder can be
associated with thyroid disease. The Tpo-Cre;Prkar1aflox/flox;Epac1-/-
(R1A-Epac1KO) mice, originally bred to investigate the role of exchange protein
directly activated by cAMP (Epac1) in follicular thyroid cancer, displayed
self-mutilating and aggressive behaviors during casual observation. To assess
these atypical responses, behavioral testing was conducted with the R1A-Epac1KO
mice, as well as their single knockout counterparts, the thyroid-specific
Prkar1a-/- and global Epac1-/- mice. Mice of all three genotypes demonstrated
increased aggressive behavior against an intruder mouse. In addition, Epac1-/-
mice increased response to an auditory stimulus, and the Prkar1a-/- and
R1A-Epac1KO mice increased swimming behavior in the Porsolt forced swim test.
Both Prkar1a-/- mice and R1A-Epac1KO mice have increased circulating thyroxine
and corticosterone concentrations. Although hyperthyroidism has not been
previously associated with aggression, increased thyroid hormone signaling might
contribute to the increased aggressive response to the intruder mouse, as well
as the increased swimming response. Mice with a genetic background of
Tpo-Cre;Prkar1aflox/flox;Epac1-/- are aggressive, and both the thyroid-specific
knockout of Prkar1a and global knockout of Epac1 likely contribute to this
aggressive behavior. This study supports the hypothesis that altered thyroid
signaling and aggressive behavior are linked.