Early-life experiences have profound effects on an individual's health. Physical and/or emotional abuse can lead to a negative sense of well-being, including behavioral problems that continue throughout life. It is estimated that youngsters and adults with history of physical and/or emotional neglect are likely to develop substance abuse, anxiety, and major depression. Though the emotional cost cannot be measured, the economic cost to society is estimated at $96 billion/year. While the mechanisms of stress response have been largely characterized in adults, little is known about the neurobiological consequences of early-life physical or emotional stress and its long-term consequences. These observations underscore the need for better understanding of the neurobiology of early-life stress and its life-long effects. The goal of this proposal is to study the role of brain's appetitive neural circuits in the long-term behavioral and biochemical consequences of stress, using a rodent model of physical (mild foot shock) versus emotional (witness foot shock) stress. This approach is novel because it focuses on appetitive regions of the brain (the nucleus accumbens and the VTA) important for motivation, reward, and psychomotor activity.
Aim 1 examines whether exposure to physical or emotional stress during the life-span influences emotional reactivity using behavioral tests designed to assess an animal's affective state, these include assessing sensitivity to: (a) drugs of abuse (cocaine, morphine), (b) natural rewards (sucrose), and (c) reactivity to anxiety-eliciting situations (open-field), and other stressors (forced swim stress).
Aim 2 assesses the biochemical integrity of this circuit, using protein biochemistry, after physical/emotional stress. This will allow for identification of gene products regulated by either form of stress, and by age, thus setting the stage for future experiments in which these identified 'stress- related'proteins will be packaged into viral vectors to study how they affect developing brain, resulting in adaptations that increase vulnerability to drugs of abuse and other behavioral disorders. Data obtained will improve our understanding of the role physical and emotional stress plays in early development in mediating pathological behavior later in life.

Public Health Relevance

Youngsters and adults with childhood history of physical and/or emotional neglect are likely to develop substance abuse, anxiety, and major depression disorders. Though the economic cost to society is estimated at $96 billion/year, little is known about the neurobiological consequences of early-life physical or emotional stress and its long-term consequences. These observations underscore the need for better understanding of the neurobiology of early-life stress and its life-long effects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA022351-02
Application #
7616802
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Thomas, David A
Project Start
2008-05-01
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2011-04-30
Support Year
2
Fiscal Year
2009
Total Cost
$237,780
Indirect Cost
Name
Florida State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
790877419
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
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Parise, Eric M; Alcantara, Lyonna F; Warren, Brandon L et al. (2013) Repeated ketamine exposure induces an enduring resilient phenotype in adolescent and adult rats. Biol Psychiatry 74:750-9
Warren, Brandon L; Vialou, Vincent F; Iñiguez, Sergio D et al. (2013) Neurobiological sequelae of witnessing stressful events in adult mice. Biol Psychiatry 73:7-14
Warren, Brandon L; Iniguez, Sergio D; Alcantara, Lyonna F et al. (2011) Juvenile administration of concomitant methylphenidate and fluoxetine alters behavioral reactivity to reward- and mood-related stimuli and disrupts ventral tegmental area gene expression in adulthood. J Neurosci 31:10347-58
Iniguez, Sergio D; Warren, Brandon L; Neve, Rachael L et al. (2010) Viral-mediated expression of extracellular signal-regulated kinase-2 in the ventral tegmental area modulates behavioral responses to cocaine. Behav Brain Res 214:460-4
Iniguez, Sergio D; Warren, Brandon L; Bolanos-Guzman, Carlos A (2010) Short- and long-term functional consequences of fluoxetine exposure during adolescence in male rats. Biol Psychiatry 67:1057-66
Wiley, Matthew D; Poveromo, Laura B; Antapasis, John et al. (2009) Kappa-opioid system regulates the long-lasting behavioral adaptations induced by early-life exposure to methylphenidate. Neuropsychopharmacology 34:1339-50
Iñiguez, Sergio D; Warren, Brandon L; Parise, Eric M et al. (2009) Nicotine exposure during adolescence induces a depression-like state in adulthood. Neuropsychopharmacology 34:1609-24
Wallace, Deanna L; Vialou, Vincent; Rios, Loretta et al. (2008) The influence of DeltaFosB in the nucleus accumbens on natural reward-related behavior. J Neurosci 28:10272-7