Parsing Distinct Aspects of the Addiction Process Using Cocaine Self-Administration, Behavioral Economics, Neuropharmacology and Neurochemistry

Abstract

In order to develop a better understanding of the neurobiological basis of cocaine addiction, scientists have begun to investigate the neural adaptations occurring in association with changes in behavior observed in animal models of addiction. Exactly how these behavioral changes relate to the addiction process, however, remains unclear. Two behavioral changes that are well documented to occur as the addiction process progresses are increased cocaine intake over time and increased time and energy devoted to obtain cocaine. The relationship between these two concepts can be addressed experimentally by performing behavioral economic analyses on cocaine self-administration data. Using behavioral economic theory, changes in cocaine intake can be investigated by studying changes in consumption when the unit-price of cocaine is relatively cheap; changes in the time and energy devoted to obtain cocaine can be studied by assessing changes in the maximal price paid for drug when the unit-price of cocaine is relatively high. The current series of studies was designed to investigate the relationship between cocaine consumption and price paid, and to further identify the neurobiological factors that cause these two distinct concepts to change over time. In the first set of studies it was discovered that changes in cocaine consumption and the price paid for cocaine can increase independently, suggesting that these two concepts are dissociable. The relationship between cocaine consumption and price paid was then addressed using neuropharmacology. It was found that drug-pretreatments can affect cocaine consumption and price paid independently, further supporting the conclusion that these two aspects of addiction are dissociable. Next, the neuropharmacological regulation of cocaine consumption was addressed. It was found that the rate and pattern of cocaine intake is tightly associated with levels of dopamine uptake inhibition which shift upward following an escalation of cocaine intake. In the final chapter, it was found that an interaction between large brain cocaine fluctuations and patterns of high-rate responding for cocaine is necessary to produce an increase in the price paid for cocaine over time. Overall, these studies suggest that cocaine consumption and price paid are dissociable phenomena that are regulated by distinct neural mechanisms.