The overall objectives of this project are to study the phenomenology, and the biochemical and neuroanatomical substrates of behavioral sensitization. This model is used to study the evolution of behavioral pathology and the role of conditioning or context-dependency in such behaviors. Environmental and pharmacological interventions are investigated in an attempt to alter the course of sensitization development and expression. Significant findings to date include demonstration of the following: 1) a novel two day cocaine sensitization paradigm which is context-dependent; 2) a second sensitization paradigm, using a three day pretreatment regimen, which is also context-dependent and is more long-lasting than the above paradigm; 3) the importance of intact dopamine function for the development, but not expression of context-dependent sensitization; 4) a role for the amygdala and nucleus accumbens in this sensitization; 5) cross sensitization between cocaine and the NMDA antagonist MK-801, and between cocaine and procaine ( a local anesthetic that is self-administered by primates), but not between cocaine and lidocaine (which is not self-administered) or cocaine and caffeine.
