The appetitive properties of cocaine are widely believed to be mediated through dopamine transmission in the mesocorticolimbic system. There is extensive evidence documenting opioid-catacholamine interactions, and it has been suggested that drugs used to treat opiate addiction may be effective in treating cocaine addiction. While naltrexone is an opioid pharmacological treatment for addiction, methylnaloxonium is a structurally similar opioid compound that may be more useful for examining dopamine turnover because it does not diffuse as readily into surrounding structures therefore making discrete central injections possible. The goal of the present study is to determine in vivo the relative efficacy of these compounds in the rat by testing the hypothesis that these compounds will differ in terms of their effects on both acute and chronic cocaine-induced extracellular dopamine and dopamine metabolite elevations in the ventral segmental area, the nucleus accumbens, and the prefrontal cortex. This will be accomplished by intracranial administration of these opioid antagonists to one mesocorticolimbic structure and the systemic administration of cocaine while simultaneously sampling from another mesocorticolimbic structure via microdialysis. The results of the study will provide scientists with a better understanding of: (l) the substrate through which opioid antagonists interfere with cocaine's rewarding effects, and (2) the relative usefulness of methylnaloxonium over naltrexone in vivo central nervous system studies of dopamine interactions.
