This application proposes to use a newly developed self-administration paradigm and fast-scan cyclic voltammetry to characterize two unique models. The two models of interest are the long-access and the break-point escalation models. The long-access escalation model reflects the escalating nature of responding and overall consumption observed in cocaine addicts. The break-point escalation model reflects the incease in motivation to take cocaine reported by addicts. The self-administration paradigm that I have developed and refined measures the lowest possible dose that will maintain cocaine responding. In this proposal, my newly developed self-administration paradigm will be used to measure changes in an animal's propensity to binge at extremely low cocaine doses following training under either the long-access escalation, break-point escalation, or a stable short-access control training model. Investigating the lowest dose for which an animal will respond following exposure to different training histories will provide novel information pertaining to the motivational aspects of cocaine self-administration in these models. The neurobiological adaptations underlying changes in the reinforcing efficacy of cocaine in either the breakpoint or the long-access escalation model remains unknown. Fast-scan cyclic volumetric allows for the high-temporal detection of extremely low levels of dopamine, which is a neurochemical that is well-accepted to be involved in the acute reinforcing effects of cocaine. Our laboratory has reported that high consumption self-administration training can result in an increased rate of dopamine reuptake at the dopamine transporter in response to cocaine. The current application further proposes to use fast scan cyclic voltammetry in order to investigate changes that may occur in dopamine reuptake in the unique models of cocaine addiction in vivo. Cocaine is one of the most addictive and highly abused drugs in the United States. Characterizing animal models can help in our neurobiological understanding of cocaine addiction, and will enable a better investigation of potential treatments for cocaine addicts.

F31DA024525

2008-01-02

2011-01-01