It is generally accepted that limited (Short Access, ShA) cocaine self-administration experience does not produce changes in brain and behavior associated with addiction. The most widely used models of addiction involve Long Access procedures (LgA, 6hrs+/day), which greatly increase the amount of drug consumption. LgA produces a number of addiction-like behaviors, and changes in brain, not seen with ShA. However, in addition to the amount of cocaine use, the temporal pattern of use ? how intermittent it is ? is also important in producing addiction-like behavior and associated neuroadaptations. Zimmer et al. (2013) developed an intermittent access self-administration procedure (IntA) to better model the intermittent patterns of cocaine use seen in addicts. He found that, despite much less total drug consumption, motivation for cocaine was higher in rats with prior IntA experience than those with LgA experience. Consistent with this, we found that IntA produces robust incentive-sensitization, as indicated by a progressive increase in cocaine demand (based on behavioral economic indicators), an associated escalation of intake, and very robust reinstatement of cocaine seeking behavior ? despite consuming much less drug than under LgA conditions. Thus, our Overall Aim is to directly compare and contrast the behavioral, psychological and neurobiological effects of these two models of addiction. The overall goal is to determine whether the changes in brain and behavior produced by LgA vs. IntA experience only differ quantitatively, or, whether there are qualitative differences in outcomes. This information will be critical in making informed decisions about the animal model to use in preclinical studies of addiction, and will also be important in determining directions in the development of therapeutics.
One challenge to the treatment and prevention of drug addiction is the need to refine and develop animal models that capture behavioral and biological patterns of compulsive drug use. While many advances have been made, recent studies suggest that the temporal pattern of drug use produces marked differences in behavioral and neural outcomes. The goal of the studies proposed here is to provide the first comprehensive comparison of two animal models of addiction in both males and females. Our focus is on alterations in dopamine and glutamate systems within the striatum and the contribution of these alterations to compulsive drug taking and drug-seeking behaviors after continuous vs. intermittent cocaine self-administration.