application): The goal of this Phase I study is to develop anti-cocaine drugs that curb cocaine's euphoria and craving. The selection criteria are that the drugs cannot be addictive themselves, nor can they produce an impairment of normal hedonic function. It is felt that drugs with these actions will be found among compounds that displace cocaine from dopamine transporter without affecting dopamine uptake per se. The approach will be to screen novel monoamine transporter ligands for hedonic and anti-cocaine actions using the Brain Stimulation Reward (BSR) curve shift paradigm. This behavioral test has a number of unique features including the ability to distinguish hedonically positive or neutral drugs from compounds with negatively hedonic actions. Behavioral results will be used to define the optimal neurochemical actions of the drugs vis-a-vis monoamine transporters. The last specific aim is to develop an animal model of craving based on IVSA reinstatement paradigm with a peripheral injection as the cue. The two series of drugs to be examined are the diphenylmethoxypiperazines (specific GBR analogs; the Nocaine-A series) that are partial cocaine agonists and a series of disubstituted piperidines (the Nocaine-B series).
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