This proposal focuses on the neuroanatomy and neurochemical control of offensive aggression. The first set of experiments will define the neural network(s), i.e., multiple populations of neurons throughout the central nervous system, that control offensive aggression. These studies will combine double and triple labeling of neurotransmitters and markers of cellular activity, together with retrograde and anterograde tracers. The neural network(s) controlling offensive aggression will be reconstructed using computer-assisted brain mapping. The functional significance of each component in the neural network will be determined by activating and blocking discrete populations of neurons. The second set of experiments will examine the interaction between vasopressin and serotonin in the control of offensive aggression. It is hypothesized that both neurotransmitter systems have reciprocal interactions that are critical for the modulation of offensive aggression - vasopressin facilitates fighting while serotonin diminishes fighting. These studies will combine site-specific microinjections of vasopressin and serotonin, immunoelectron microscopy to verify synaptic connections between vasopressin neurons and serotonin terminals, and labeling neurons that have both serotonin and vasopressin receptors. Violence in the United States is a national health problem. The studies outlined in this proposal should enhance our understanding of the neuroanatomy and neurochemical control of offensive aggression. There is evidence that the neural network controlling aggression is not static, but plastic; changes in environmental conditions continuously reshape pre- and postsynaptic elements to enhance and depress agonistic behavior. The predisposition toward aggressive and submissive behavior in certain environments may be mediated, in part, by alterations in the chemistry and synaptic connections between neurotransmitter systems. It is critical that we understand the environmental and biological conditions that influence agonistic behavior. Only then can we devise rational psychosocial and pharmacological therapies to help the victims of violent behavior and to understand better the neurobiology of individuals predisposed to violent behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH052280-04
Application #
2675208
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1995-09-30
Project End
1999-04-30
Budget Start
1998-05-09
Budget End
1999-04-30
Support Year
4
Fiscal Year
1998
Total Cost
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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