This proposal examines the interaction between the brain and a stressful environment during the developmental period of adolescence. It is well documented that perinatal stressors can affect brain development resulting in long-term neurobiological and behavioral consequences. However, little is known about the biological consequences of stress in adolescence. There are reports that adolescents between 12-15 are ranked third in victimization rate while adolescents between 16-19 are the most victimized group in the population. In an animal model, peripubertal or adolescent male hamsters exposed to the stress of threat and attack from larger hamsters present with altered agonistic behavior as young adults when compared to their sibling controls. In addition, adult animals with a history of adolescent stress have altered brain chemistry, specifically, the arginine vasopressin (AVP) and serotonin (5-HT) innervation to the hypothalamus involved in the regulation of agonistic behavior. This work asks three questions: (1) how has adolescent stress affected the AVP and 5-HT systems; (2) are the behavioral and neurobiological changes caused by stress in adolescence different from those caused by stress in adulthood; and (3) are the changes in neurobiology and behavior from adolescent stress permanent? Stress-induced changes in the AVP and the 5-HT systems are determined by measures of gene transcription, receptor binding, and neurotransmitter release with microdialysis; the behavior and neurobiology of siblings exposed to stress during adolescence or adulthood are compared to age matched sibling controls; and animals stressed in adolescence are examined over several months for recovery of behavior and neurobiology. This work will help understand the effects of stress in adolescence and the ability of the brain to recover from insult at this potentially vulnerable period of development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH052280-07
Application #
6530845
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Lyon, Reid G
Project Start
1995-09-30
Project End
2005-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
7
Fiscal Year
2002
Total Cost
$227,529
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Psychiatry
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Ferris, Craig F; Stolberg, Tara; Kulkarni, Praveen et al. (2008) Imaging the neural circuitry and chemical control of aggressive motivation. BMC Neurosci 9:111
Brevard, Mathew E; Kulkarni, Praveen; King, Jean A et al. (2006) Imaging the neural substrates involved in the genesis of pentylenetetrazol-induced seizures. Epilepsia 47:745-54
Ferris, Craig F; Lu, Shi-Fang; Messenger, Tara et al. (2006) Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior. Pharmacol Biochem Behav 83:169-74
Ferris, Craig F; Kulkarni, Praveen; Sullivan Jr, John M et al. (2005) Pup suckling is more rewarding than cocaine: evidence from functional magnetic resonance imaging and three-dimensional computational analysis. J Neurosci 25:149-56
Ferris, Craig F (2005) Vasopressin/oxytocin and aggression. Novartis Found Symp 268:190-8; discussion 198-200, 242-
Ferris, Craig F (2003) Using an animal model to assess the long-term behavioral and biological consequences of adolescent abuse and exposure to alcohol. Ann N Y Acad Sci 1008:69-78
King, Jean A; Messenger, Tara; Ferris, Craig F (2002) Seed finding in golden hamsters: a potential animal model for screening anxiolytic drugs. Neuropsychobiology 45:150-5
Ferris, C F; Rasmussen, M F; Messenger, T et al. (2001) Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder. BMC Neurosci 2:10
Delville, Y; De Vries, G J; Ferris, C F (2000) Neural connections of the anterior hypothalamus and agonistic behavior in golden hamsters. Brain Behav Evol 55:53-76
Ferris, C F (2000) Adolescent stress and neural plasticity in hamsters: a vasopressin-serotonin model of inappropriate aggressive behaviour. Exp Physiol 85 Spec No:85S-90S

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