Cocaine addicted individuals persistently seek and take cocaine, and have an inability to inhibit these behaviors, despite the knowledge of adverse consequences. The specific neural mechanisms that underlie cocaine addiction are still unclear, and require further research. The proposed research plan explores a new hypothesis that potentially explains how specific adaptations in the nucleus accumbens, and related circuitry, result in addiction. Briefly, the hypothesis observes that most accumbal neurons are inhibited under cocaine exposure, and become chronically hypoactive with repeated cocaine exposure. However, the set of neurons that respond to cocaine-related events (ie: cues, lever presses) during a self-administration session maintain their firing rates during cocaine exposure, and therefore do not become chronically hypoactive with repeated exposure. In this way, these neurons gain an enhanced influence over accumbal signaling, which facilitates further cocaine-seeking and taking. Using chronic electrophysiological techniques, the present proposal is designed to test several predictions of this hypothesis, while also integrating with and contributing to the present body of literature on accumbal function. Relevance: Cocaine addiction exacts enormous financial, social, and public health tolls on our society, as well as large personal tolls on the addicted individuals, their families, and their friends. The present set of experiments will examine how cocaine alters the responses of neurons in the brain's reward circuits. A more complete understanding of the actions of cocaine is ultimately expected to contribute to the development of effective treatments for cocaine addiction. ? ? ? ?
| Guillem, Karine; Kravitz, Alexxai V; Moorman, David E et al. (2010) Orbitofrontal and insular cortex: neural responses to cocaine-associated cues and cocaine self-administration. Synapse 64:1-13 |
| Kravitz, Alexxai V; Peoples, Laura L (2008) Background firing rates of orbitofrontal neurons reflect specific characteristics of operant sessions and modulate phasic responses to reward-associated cues and behavior. J Neurosci 28:1009-18 |
| Peoples, L L; Kravitz, A V; Guillem, K (2007) The role of accumbal hypoactivity in cocaine addiction. ScientificWorldJournal 7:22-45 |
