Stress influences a wide range of behaviors, and prolonged stress can induce or exacerbate psychiatric disorders. Stress is believed to exert a greater impact in adolescents than adults. One target for the effects of stress on behavior is the amygdala, a brain region involved with the production of emotion. The goal of this research is to understand the impact of prolonged stress on behavior. Specifically, the short term goal is to understand how chronic stress affects behavior through actions on amygdala neurons, and how this relates to age-dependent effects of stress. This proposal examines the hypothesis that chronic stress exaggerates affective behavior by increasing the excitability of amygdala neurons, and that this effect is greater in adolescence. This hypothesis will be tested by 1) quantifying the effects of chonic stress on amygdala neuronal excitability in vivo and in vitro, 2) determining the underlying disruption of ion channels, 3) quantifying the effects of chronic stress on amygdala neuronal integration and amygdala-dependent behaviors, such as Pavlovian conditioning, and 4) comparing these effects of chronic stress between adolescence and adulthood. This will be studied using a combination of in vivo and in vitro electrophysiological recordings and single-cell calcium imaging of amygdala neurons in a chronic stress model. Measures of membrane excitability and behavioral measures of Pavlovian fear conditioning will be quantified, and compared between groups with a 2-way ANOVA and appropriate post-hoc comparisons. It is expected that chronic stress will increase the excitability of amygdala neurons by a specific chennelopathy, and exaggerate amygdala-dependent behaviors, and this effect will be greater in adolescence than adulthood. This study can demonstrate a mechanism whereby stress increases affective behaviors in an age-dependent manner. By understanding the effects of chronic stress, and its age-dependency, one can potentially gain insight into a means to prevent or reverse stress-induced deficiencies in different age groups. Chronic stress, such as abuse and conflict, can contribute to psychiatric disorders, and can be particularly harmful in children. This study will examine if chronic stress exerts a bigger effect in young animals on a brain region involved with emotional behavior, the amygdala. This would provide an understanding of why adolescents are more vulnerable to some effects of stress, which can lead to age-appropriate preventative or curative measures.

Public Health Relevance

Chronic stress, such as abuse and conflict, can contribute to psychiatric disorders, and can be particularly harmful in children. This study will examine if chronic stress exerts a bigger effect in young animals on a brain region involved with emotional behavior, the amygdala. This would provide an understanding of why adolescents are more vulnerable to some effects of stress, which can lead to age-appropriate preventative or curative measures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH084970-05
Application #
8461992
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Panchision, David M
Project Start
2009-07-07
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2013
Total Cost
$329,314
Indirect Cost
$115,474
Name
Rosalind Franklin University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
069501252
City
North Chicago
State
IL
Country
United States
Zip Code
60064
Zhang, Wei; Rosenkranz, J Amiel (2016) Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala. Neuropsychopharmacology 41:2309-23
Adams, Thomas; Rosenkranz, J Amiel (2016) Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala. Neuropsychopharmacology 41:1929-40
Padival, M A; Blume, S R; Vantrease, J E et al. (2015) Qualitatively different effect of repeated stress during adolescence on principal neuron morphology across lateral and basal nuclei of the rat amygdala. Neuroscience 291:128-45
Jaisinghani, Suraj; Rosenkranz, J Amiel (2015) Repeated social defeat stress enhances the anxiogenic effect of bright light on operant reward-seeking behavior in rats. Behav Brain Res 290:172-9
Hetzel, Andrea; Rosenkranz, J Amiel (2014) Distinct effects of repeated restraint stress on basolateral amygdala neuronal membrane properties in resilient adolescent and adult rats. Neuropsychopharmacology 39:2114-30
Zhang, Wei; Hetzel, Andrea; Shah, Bijal et al. (2014) Greater physiological and behavioral effects of interrupted stress pattern compared to daily restraint stress in rats. PLoS One 9:e102247
Padival, M A; Blume, S R; Rosenkranz, J A (2013) Repeated restraint stress exerts different impact on structure of neurons in the lateral and basal nuclei of the amygdala. Neuroscience 246:230-42
Padival, Mallika; Quinette, Danielle; Rosenkranz, J Amiel (2013) Effects of repeated stress on excitatory drive of basal amygdala neurons in vivo. Neuropsychopharmacology 38:1748-62
Yusufishaq, Shabana; Rosenkranz, J Amiel (2013) Post-weaning social isolation impairs observational fear conditioning. Behav Brain Res 242:142-9
Zhang, Wei; Rosenkranz, J Amiel (2013) Repeated restraint stress enhances cue-elicited conditioned freezing and impairs acquisition of extinction in an age-dependent manner. Behav Brain Res 248:12-24

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