Psychostimulant addiction poses a significant burden on our society, afflicting millions of Americans, and has proven difficult to treat possibly becaus of the complexity of the disorder. Many behavioral procedures have been developed to model the addiction process in several species including non-human primates and rats. The neuropeptide orexin, made exclusively in the hypothalamus, has been shown to play an important role in both motivational responding for cocaine and the association of drug reward with predictive cues. The goal of the present proposal is to better understand the importance of this system in the progression of the addiction process. Two different patterns of cocaine exposure, intermittent access and long access, will be used that produce increased cocaine demand and seeking in rats. The role of orexin signaling in the elevated cocaine demand and seeking after these different exposures to cocaine will be used to reveal the role of orexin neurons in the excessive demand for cocaine that occurs with addiction. This research will also identify afferents to the orexin cell field that are involved in cocaine abuse. This proposed research involves a brain system (orexin) and several techniques that are new for me, and learning these modern neuroscience methods will train me in how to examine and manipulate specific brain circuits to identify their roles in the addiction process. This training will be criical to my future development as a research neuroscientist in addiction.
Using cocaine leads to changes in brain circuits that process reward and direct our behavior to obtain rewarding stimuli. An understanding of how cocaine exposure changes these brain circuits is important because it could provide new therapeutic targets to treat drug addiction.
