The entrainment, generation and expression of circadian rhythms can be disrupted by social stress. In this project, a resident-intruder social conflict paradigm with hamsters will be used to study the relationship between circadian rhythms and social stress. Hamsters are spontaneously aggressive animals, and an animal that has been repeatedly defeated by an aggressive conspecific will eventually become defensive/submissive when exposed to a nonaggressive opponent. A resident animal that will not defend its home cage territory against an intruder will be categorized as a conditioned defeat (CD) animal. In a series of experiments, we will employ the CD paradigm to investigate potential pharmacological agents (diazepam and melatonin) that can influence circadian rhythms. Different lighting schedules, the timing of drug administration, and melatonin secretion will be investigated. The following aims will be addressed.
Specific Aim 1 - we will determine if constant (24 hours) light or dark can have an influence on CD.
Specific Aim 2 - we will determine if low dose of diazepam (1.0 mg/kg IP) during different lighting conditions can effectively attenuate CD.
Specific Aim 3 - we will focus on melatonin functioning: 1. we will determine if exogenous administration of melatonin (20 mg/kg IP) can attenuate CD; 2. we will determine if CD can have an influence on endogenous levels of melatonin; and 3. we will explore if melatonin secretion is controlled by dopamine. This project will explore the underlying neural mechanisms that can affect circadian rhythms during social stress.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Pulliam, John V K; Xu, Zhenfeng; Ford, Gregory D et al. (2013) Computational identification of conserved transcription factor binding sites upstream of genes induced in rat brain by transient focal ischemic stroke. Brain Res 1495:76-85
Li, Yonggang; Lein, Pamela J; Liu, Cuimei et al. (2012) Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury. Toxicol Appl Pharmacol 262:194-204
Rodriguez-Mercado, Rafael; Ford, Gregory D; Xu, Zhenfeng et al. (2012) Acute neuronal injury and blood genomic profiles in a nonhuman primate model for ischemic stroke. Comp Med 62:427-38
Mong, Jessica A; Baker, Fiona C; Mahoney, Megan M et al. (2011) Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones. J Neurosci 31:16107-16
Guo, Qingmin; Wang, Guangming; Namura, Shobu (2010) Fenofibrate improves cerebral blood flow after middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 30:70-8
Davidson, Alec J; Castanon-Cervantes, Oscar; Leise, Tanya L et al. (2009) Visualizing jet lag in the mouse suprachiasmatic nucleus and peripheral circadian timing system. Eur J Neurosci 29:171-80
Wang, Guangming; Guo, Qingmin; Hossain, Mohammed et al. (2009) Bone marrow-derived cells are the major source of MMP-9 contributing to blood-brain barrier dysfunction and infarct formation after ischemic stroke in mice. Brain Res 1294:183-92
Paul, Ketema N; Laposky, Aaron D; Turek, Fred W (2009) Reproductive hormone replacement alters sleep in mice. Neurosci Lett 463:239-43
Guo, Qingmin; Wang, Guangming; Liu, Xiaowei et al. (2009) Effects of gemfibrozil on outcome after permanent middle cerebral artery occlusion in mice. Brain Res 1279:121-30
Fukuhara, Chiaki; Tosini, Gianluca (2008) Analysis of daily and circadian gene expression in the rat pineal gland. Neurosci Res 60:192-8

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