A major consequence of cocaine self-administration is an increased awareness of the sensory surround, and heightened sensory perception actions which most likely contribute to an overall positive drug experience. Despite the likelihood that these effects add 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 information along primary sensory pathways leading to the neocortex. These experiments will be conducted in intact, anesthetized rats and will employ combinations of single cell extracellular recording, systemic and local (microiontophoretic) methods of drug administration, activation of peripheral sensory pathways, electrical stimulation of monoaminergic pathways and computer assisted analysis of peri-event histograms and cumulative rasters to evaluate interactions between cocaine and sensory thalamic and cortical neuronal responses to synaptic inputs or putative transmitter substances. Because of its interactions with noradrenergic and serotonergic systems which have been shown to modulate specific parameters of sensory neuron function, we postulate that cocaine will enhance signal transmission along ascending sensory pathways. In order to test this idea the current proposal establishes three major goals: 1) determine the effects of systemically administered cocaine on response threshold and receptive field properties of rat somatosensory cortical neurons, 2) determine the effects of cocaine on transmission of sensory information through thalamocortical circuits and 3) characterize and quantify the effects of cocaine on thalamic and cortical neuron responses to phasic activation of noradrenergic and serotonergic pathways. Completion of this work will not only clarify how cocaine influences sensory stimulus coding properties of sensory neurons, but will also provide a foundation for predicting how sensory circuits would perform when cocaine is self- administered. As such these studies will establish a much needed link between the cellular actions of cocaine in sensory circuits and behavioral data which suggests a prominent effect of the drug on sensory perception.
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