The goal of the present proposal is to provide an analysis of the effects of a major drug of abuse, cocaine, on basic aspects of perceptual and motor function in nonhuman primates. The proposed work focuses on an animal model of hearing that uses biologically relevant sounds (i.e., speech) containing acoustic features that are critical for the perception of sounds in general, and for the underlying neural processing of acoustic stimuli by the auditory nervous system. This proposal's aims are to employ the developed perceptual discrimination procedures as a model for precisely determining the nature of cocaine's effects on fundamental perceptual-motor processes, and to relate these effects to possible dopamine (DA) receptor subtypes. One set of experiments will employ specially-synthesized speech stimuli which will provide precise control over the difficulty of the discriminations, and also allow us to relate cocaine's effects to explicit changes in perceptual thresholds for detecting changes in the spectral characteristics of speech. In a second set of experiments, the specificity of cocaine's effects on speech perception will be examined by measuring cocaine's effects when simple tones are substituted for the spectrally complex speech stimuli. A third set of experiments will relate the effects of cocaine on speech perception and reaction times to current knowledge regarding DA receptor subtypes by examining whether other DA agonists (selective for both D1-type and D2/D3-type receptors) may also elicit cocaine's stimulant-like effects on reaction times, or its adverse effects on speech discriminations. A fourth set of experiments will determine whether cocaine-induced reductions in the accuracy of speech perception may be attributed to effects on memory. This research will provide fundamental data on cocaine's effects on perceptual and motor functions in nonhuman primates across a range of doses, and its likely mechanisms of action via the DA system. The research will yield information directly relevant to the clinical implications of the perceptual/motor effects of cocaine use.
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