Psychostimulant addiction poses a significant burden on our society, afflicting millions ofAmericans, and has proven difficult to treat, possibly because of the complexity of the disorder.Many behavioral procedures have been developed to model the addiction process in severalspecies including non-human primates and rats. The neuropeptide orexin, made exclusively inthe hypothalamus, has been shown to play an important role in both motivational responding forcocaine and the association of drug reward with predictive cues. The goal of the presentproposal is to better understand the importance of this system in the progression of theaddiction process. Two different behavioral procedures will be used that produce phenotypesassociated with increased drug seeking in rats. An array of techniques will be employed tounderstand the function of the orexin system in rats experiencing these behavioral procedures.These techniques include histology and immunohistochemistry, intra-cranial pharmacology, andadministration of vivo-morpholinos to suppress orexin protein expression. Using thesetechniques to understand the role the orexin system plays in these behavioral procedures willgreatly increase our understanding of the underlying neurobiology associated with theprogression of the addiction process. This research will identify a number of targets for potentialpharmacological treatments. These are all new techniques for me, and learning these modernneuroscience methods will train me in how to examine and manipulate specific brain circuits toidentify their roles in the addiction process. This training will be critical to my future developmentas a research neuroscientist in addiction.
Using cocaine leads to changes in brain circuits that process reward and direct our behavior to obtainrewarding stimuli. An understanding of how cocaine exposure changes these brain circuits is importantbecause it could provide new therapeutic targets to treat drug addiction.