Cocaine addiction is a national health problem with over three million cocaine abusers in need of treatment. The problem is particularly insidious because of the relapse due to environmentally evoked cocaine 'craving.' To date there are no therapeutic agents to prevent cocaine relapse. Indeed the key to understanding cocaine relapse is identifying the neuroanatomyand neuro chemical mechanisms in the central nervous system contributing to cue-evoked craving. Neurotensin (NT) is a neuropeptide in the central nervous system closely linked to the dopaminergic mesocorticolimbic system. This dopaminergic system is involved in the neurological and behavioral changes associated with cocaine self-administration, withdrawal and reinstatement, i.e. cocaine craving. Neurotensin is thought to exert an inhibitory regulation on mesocorticolimbic thnction. This proposal will investigate the hypothesis that chronic cocaine exposure alters brain activity and NT's regulatory role on doparninergic facilitation of reinstatement. The studies outlined in this proposal will use functional magnetic resonance imaging (fMRI) in conscious rats to study changes in brain activity with cocaine administration and reinstatement. MRI will also be used to examine site-specific changes in NT binding during cocaine self-administration, withdrawal and reinstatement. With a newly developed paramagnetic NT ligand, it is possible to follow cocaine-associated changes in NT receptors in the same animals over several weeks. With this repeated 'in vivo autoradiography,' it is possible to correlate changes in cocaine associated brain activity with discrete changes in NT binding in the mesocorticolimbic system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA013517-04
Application #
6781013
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Aigner, Thomas G
Project Start
2001-09-30
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
4
Fiscal Year
2004
Total Cost
$371,430
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Psychiatry
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Kulkarni, Praveen; Stolberg, Tara; Sullivanjr, J M et al. (2012) Imaging evolutionarily conserved neural networks: preferential activation of the olfactory system by food-related odor. Behav Brain Res 230:201-7
Febo, Marcelo; Segarra, Annabell C; Stolberg, Tara L et al. (2011) BOLD signal response to cocaine varies with sexual receptivity in female rats. Neuroreport 22:19-22
Ferris, Craig F; Stolberg, Tara (2010) Imaging the immediate non-genomic effects of stress hormone on brain activity. Psychoneuroendocrinology 35:5-14
Febo, Marcelo; Akbarian, Schahram; Schroeder, Frederick A et al. (2009) Cocaine-induced metabolic activation in cortico-limbic circuitry is increased after exposure to the histone deacetylase inhibitor, sodium butyrate. Neurosci Lett 465:267-71
Febo, Marcelo; Shields, Jessica; Ferris, Craig F et al. (2009) Oxytocin modulates unconditioned fear response in lactating dams: an fMRI study. Brain Res 1302:183-93
Nephew, Benjamin C; Caffrey, Martha K; Felix-Ortiz, Ada C et al. (2009) Blood oxygen level-dependent signal responses in corticolimbic 'emotions' circuitry of lactating rats facing intruder threat to pups. Eur J Neurosci 30:934-45
Febo, Marcelo; Stolberg, Tara L; Numan, Michael et al. (2008) Nursing stimulation is more than tactile sensation: It is a multisensory experience. Horm Behav 54:330-9
Ferris, Craig F; Stolberg, Tara; Kulkarni, Praveen et al. (2008) Imaging the neural circuitry and chemical control of aggressive motivation. BMC Neurosci 9:111
Luo, Feng; Li, Zhixin; Treistman, Steven N et al. (2007) Confounding effects of volatile anesthesia on CBV assessment in rodent forebrain following ethanol challenge. J Magn Reson Imaging 26:557-63
Sicard, Kenneth M; Henninger, Nils; Fisher, Marc et al. (2006) Long-term changes of functional MRI-based brain function, behavioral status, and histopathology after transient focal cerebral ischemia in rats. Stroke 37:2593-600

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