DOPAMINE RESPONSE TO PREDICTED AND UNPREDICTED COCAINE

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Dopamine neurotransmission is commonly associated with positive reinforcement derived from many sources. Recently, however, an accumulation of relevant studies suggest that dopamine may serve as a general activation signal that accentuates various types of neural information, including those that are clearly not rewarding. In addition, increased dopamine neurotransmission is thought to provide neural emphases to various stimuli that are biologically relevant, thus increasing the influence that such stimuli have upon the organism. Although evidence to the contrary is substantial, there is momentum toward the view that the involvement of dopamine in positive reinforcement may be coincidental to the positive aspect of the stimuli and more reflective of its biological importance. For instance, dopamine neurons respond to cues predictive of cocaine or other positive reinforcement, but also to stimuli of dissimilar importance. These findings have provided a new impetus to examine dopamine and drug abuse, and has direct relevance to behavioral paradigms in drug abuse research. For example, behavioral conditioning to cocaine involves the repeated administration of the drug. While it is frequently assumed that different modes of drug administration have the same overall effects, emerging sentiments on the role of dopamine would lead us to believe otherwise. Consistent with this view, animals expecting cocaine administration (e.g., as during cued infusions or self- administration), and animals receiving unexpected cocaine injections (random or non-cued drug infusions) would have contrasting neural experiences. Although both modes of cocaine administration result in behavioral conditioning, the timing of dopamine activation, and even the biological relevance attached to each experience may be distinctively different. In support of this view, preliminary data presented in this proposal show the presence of cocaine-associated cues potentiate cocaine-stimulated levels of nucleus accumbens dopamine and locomotor activity. These differences may impact directly on incentive properties inspired by cocaine use, and hence, the level of motivation supporting drug-seeking and drug-taking behaviors. Using a model of cued and random cocaine infusion in conjunction with in vivo microdialysis and behavioral activity assessment, the proposed research will determine how predictable and unpredictable cocaine delivery affects levels of dopamine and locomotion. In addition, data from animals naive to a particular cue will determine whether novel stimuli affect dopamine-mediated responses.