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.
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