The proposed research will investigate the effects of cocaine on aspects of sensory and motor function in nonhuman primates. Past research in this laboratory has employed combined behavioral pharmacology and animal psychophysical techniques to characterize the effects of acute and chronic administrations of cocaine on hearing, vision, and reaction time performances. This work has demonstrated that 1) cocaine can facilitate the speed of performing of a simple motor response (""""""""reaction time"""""""") in nonhuman primates; 2) these effects occur in the absence of changes in sensitivity to auditory or visual stimuli signalling the motor response; and 3) cocaine adversely affects the discrimination of human speech sounds. The proposed research will extend this previous work by conducting studies to determine the conditions under which cocaine may enhance reaction time performances, whether such enhancements are of a sensory or motor nature, and the nature of the decrease in the discriminability of speech sounds following cocaine. One set of experiments will examine the role of sensitization and/or tolerance in cocaine's effects on sensory/motor function by a) replicating acute dose-effect functions for sensory/motor performances after an intervening period of chronic cocaine dosing, and b) comparing the effects of pre-session versus post-session daily cocaine administrations. A second set of experiments will examine the contribution of sensory and motor components to the demonstrated effects of cocaine's shortening reaction time performances by a) assessing whether cocaine can produce an increase in response speed in the absence of a 'triggering' discriminative stimulus (S-D); and b) determining whether or not cocaine may improve a motor performance that is already near optimal. A third set of experiments will examine cocaine's adverse effects on vowel discriminations to determine a) whether the effect occurs under different stimulus detection procedures, and b) whether cocaine's effects on vowel discriminations may be due to a shift in threshold sensitivity in the auditory frequency range of normal human vowel sounds. A fourth set of experiments will relate the stimulant effects of cocaine to current knowledge regarding DA receptor subtypes by examining whether other DA agonists (selective for both D1 and D2 receptors) may also elicit cocaine's stimulant-like effects on reaction times, or its adverse effects on speech sound discriminations. This research will provide fundamental data on cocaine's effects on sensory and motor function across a range of doses. Both acute and chronic drug administration schedules will be examined, and the research will yield information directly relevant to the clinical implications of the sensory/motor effects of cocaine use.
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