The limiting factor in the treatment of drug addiction is the high rate of relapse seen in addicts, despite costly treatment interventions. Craving for the drug long after the initiation of abstinence is argued to be a primary contributor to this recidivism. Relapse is often preceded by subjective reports of intense craving for the drug. Such craving can be induced in an individual by the presentation of stimuli previously associated with their drug taking experiences. Cue-induced craving is modeled in procedures using rats wherein rats will press a lever for the presentation of a stimulus complex (a tone + light) previously associated with their drug taking. We have recently demonstrated (Nature, 412:141-2, 2001.) that responding for a stimulus previously associated with cocaine self-injections increases progressively over the course of withdrawal from self-administration (13-fold increase by day 60 of withdrawal). We have labeled the phenomenon an """"""""incubation of craving"""""""". We have also recently observed the incubation of craving effect in rats responding for a stimulus previously associated with orally self-administered sucrose. The experiments outlined in this proposal will explore the neuroanatomical substrates of the incubation of craving effect in both cocaine- and sucrose-experienced animals. The basolateral amygdala and the nucleus accumbens will be examined in this regard using a procedure of reversible inactivation of each structure prior to testing at the different withdrawal time points. All experiments in this proposal are designed to allow full participation of undergraduate and master's level students in an area of research usually reserved for Ph.D. students and post-doctoral researchers. These experiments provide an initial examination of the incubation of craving effect and will influence the direction of a future RO1 proposal from my laboratory. Information gained from this project will provide direction for behavioral therapy and medications-based therapy for craving and relapse. ? ?
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