A major consequence of cocaine self-administration is heightened sensory perception, an action which most likely contributes to an overall positive drug experience. Despite the likelihood that this effect adds to cocaine's desirability as a recreational compound and plays a supporting role in drug craving and abuse potential, few studies have investigated the neural substrates underlying cocaine's influence on sensory information processing. The fundamental question to be addressed in the proposed project is how cocaine affects the transmission of afferent sensory signals to a primary sensory circuit within the neocortex. These experiments will be conducted in intact, anesthetized rats and will employ combinations of single cell extracellular recording, systemic and local (microiontophoretic or micropressure) methods of drug administration, activation of cortical afferent pathways, procedures for depletion of central monoamines and computer assisted analysis of peri-event histograms to evaluate interactions between cocaine and somatosensory cortical neuronal responses to synaptic inputs or putative transmitter substances. The hypothesis to be tested is that because of its well established effects on monoaminergic systems which project extensively to sensory areas of the brain including those in the cerebral cortex and because of the modulatory actions of these systems on sensory cortical function, cocaine should exert monoamine-like changes in cortical neuronal responsiveness to afferent sensory signals. In preliminary studies cocaine has already been shown to produce noradrener- gic- like facilitating effects on cortical unit responses to thalamocortical synaptic inputs and glutamate. After characterizing the effects of systemically-administered cocaine on somatosensory unit responses to synaptic stimuli, three specific issues will be addressed regarding the neural substrates responsible for these actions: 1) the cortical or sub-cortical site of these actions, 2.) their dependence on endogenous monoamines and 3.) their pharmacological specificity with respect to other cocaine-like substances. The goal of this work will be to define the actions of cocaine at the synaptic level within a monoaminergically-innervated sensory circuit of the mammalian brain. Such studies win provide much needed information concerning the physiological basis of the drug's """"""""desirable"""""""" effects on sensory information processing and as such may lead to new strategies for treating and preventing cocaine addiction.
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