Uncontrolled aggressive behavior is a serious social problem. Several rodent models of aggression have been developed to understand the neurobiological bases of aggression with the goal of developing pharmacological interventions. One common feature of these rodent models of aggression is that brain serotonin concentrations tend to be inversely correlated with aggressive behavior. A new model of intense, unrelenting aggression has been developed using mice that have the gene encoding the neuronal isoform of nitric oxide synthase (nNOS) selectively deleted. Male nNOS-/- mice display persistent aggression against other males, and persistent mounting attempts toward wild-type (WT) anestrous females. Female nNOS-/- mice do not display elevated agonistic behaviors in intruder-resident or neutral arena tests of aggression. The goal of the proposed studies is to examine the sex difference in aggressive behavior of nNOS-/- mice, and to determine the contribution of serotonin in aggressive behavior of nNOS-/- mice. There are four specific aims of the proposed studies: (1) to use a pharmacological manipulation, 7-nitroindazole (a specific nNOS antagonist), to confirm the observation that nNOS is important in mediating aggression, (2) to determine the contribution of sex steroid hormones to the sex difference in aggressive behavior among nNOS-/- mice, (3) to establish if female nNOS-/- mice display increased maternal aggression relative to WT mice, and (4) to determine the role of serotonin in the mediation of aggression in nNOS-/- animals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH057760-03
Application #
6185828
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1998-08-01
Project End
2001-06-30
Budget Start
2000-08-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$54,418
Indirect Cost
Name
Johns Hopkins University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Benderlioglu, Zeynep; Dow, Eliot (2017) Low temperatures during ontogeny increase fluctuating asymmetry and reduce maternal aggression in the house mouse, Mus musculus. Ethology 123:442-452
Benderlioglu, Zeynep; Dow, Eliot; Pyter, Leah M (2007) Neonatal exposure to short days and low temperatures blunts stress response and yields low fluctuating asymmetry in Siberian hamsters. Physiol Behav 90:459-65
Nelson, Randy J; Trainor, Brian C; Chiavegatto, Silvana et al. (2006) Pleiotropic contributions of nitric oxide to aggressive behavior. Neurosci Biobehav Rev 30:346-55
Benderlioglu, Zeynep; Eish, Jenny; Weil, Zachary M et al. (2006) Low temperatures during early development influence subsequent maternal and reproductive function in adult female mice. Physiol Behav 87:416-23
Nelson, Randy J (2005) Effects of nitric oxide on the HPA axis and aggression. Novartis Found Symp 268:147-60; discussion 160-6, 167-7
Hotchkiss, Andrew K; Pyter, Leah M; Gatien, Michelle L et al. (2005) Aggressive behavior increases after termination of chronic sildenafil treatment in mice. Physiol Behav 83:683-8
Gotti, Stefano; Chiavegatto, Silvana; Sica, Monica et al. (2004) Alteration of NO-producing system in the basal forebrain and hypothalamus of Ts65Dn mice: an immunohistochemical and histochemical study of a murine model for Down syndrome. Neurobiol Dis 16:563-71
Benderlioglu, Zeynep; Sciulli, Paul W; Nelson, Randy J (2004) Fluctuating asymmetry predicts human reactive aggression. Am J Hum Biol 16:458-69
Benderlioglu, Zeynep; Nelson, Randy J (2004) Digit length ratios predict reactive aggression in women, but not in men. Horm Behav 46:558-64
Benderlioglu, Zeynep; Nelson, Randy J (2004) Season of birth and fluctuating asymmetry. Am J Hum Biol 16:298-310

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