The primary long-range objective is to elucidate and characterize the actions of drugs of abuse as they influence and modify neuronal function. One of the crucial damaging aspects of drug addiction is the persistent wanting, or craving, that remains following rehabilitation. This contributes to relapse and a high failure rate in attempts to treat addiction. Because craving persists long after the cessation of withdrawal and recovery from tolerance, it is often suggested that a drug-induced neural plasticity has occurred within the circuitry of the brain. These changes maintain the potential for future triggering of drug craving. Although the neural underpinnings of the """"""""craving circuitry"""""""" of the brain are beginning to be unraveled, much remains to be determined. The hippocampus is a region of the brain involved with memory formation and is crucial for the performance of several associative learning and memory tasks. The administration of addictive substances directly into the hippocampus has been shown to support self administration behavior, and the activation of this brain region can prime, or reinstate, drug seeking behavior in animal models of addiction. Investigating the actions of drugs of abuse in the hippocampus is therefore merited. Electrophysiological recording techniques will be used to monitor neuronal responses from the in vitro hippocampal slice preparation. The acute and persisting effects of cocaine on the induction of various forms of synaptic plasticity and neurotransmission will be assessed. The central hypothesis is that the neural adaptations resulting from exposure to drugs of abuse likely include modifications of the normal synaptic plasticity mechanisms typically utilized to store information within neuronal networks.
of this research is for providing guiding information and principles concerning the understanding of both the normal processes and the drug-induced changes involved in the long-term consequences of drug exposure in the neural circuitry of the brain. In this application, a novel mechanism for cocaine actions underlying the plasticity of synaptic plasticity (i.e. metaplasticity) in the hippocampal formation will be investigated, and the subsequent effects of exposure to cocaine on such processes will be assessed. Determining how metaplasticity may contribute to the persistence of craving/relapse will point the way toward relevant clinical approaches to the treatment of addiction.
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