Cocaine Modulation of Sensory Neuron Function

Waterhouse, Barry

Abstract

Short term consequences of acute cocaine self-administration include increased awareness of the sensory surround and heightened sensory perception; actions which most likely contribute to an overall positive drug experience. Likewise, it is becoming increasingly clear that a significant component of the """"""""drug craving"""""""" which develops in conjunction with chronic cocaine use involves the establishment of strong associations between drug related environmental cues and drug-induced feelings of well being and euphoria. Despite the likelihood that cocaine's effects on sensory signal processing add to the drug's desirability as a recreational compound and play a role in the establishment of drug craving, few studies have systematically investigated the impact of cocaine on sensory neuron function. The fundamental question to be addressed in the proposed project is how cocaine affects the receptive field properties of individual neurons along primary sensory pathways leading to the neocortex. Experiments will be conducted in intact, anesthetized rats and will employ combinations of single unit extracellular recording, systemic and local (microiontophoretic) methods of drug administration, peripheral activation of sensory pathways, and computer assisted analysis of perievent histograms and cumulative raster records to evaluate interactions between cocaine and sensory thalamic and cortical neuronal responses to synaptic inputs or putative transmitter substances. Because of its well known interactions with noradrenergic and serotonergic systems which have been shown to modulate specific parameters of sensory neuron function, we postulate that cocaine will promote a net facilitation of signal transfer along ascending sensory pathways. In previous periods of support we have determined the timecourse, dose dependency and pharmacological specificity of a range of effects of cocaine on somatosensory thalamic and cortical neuron responsiveness to peripheral tactile stimulation. In order to continue this line of investigation the current proposal establishes two major goals: 1) determine the effects of acute systemically administered cocaine on receptive field properties of neurons in selected thalamic and cortical subregions of the rat trigeminal somatosensory network, and 2) examine sensory neuron function in animals chronically treated with cocaine. Completion of this work will not only clarify how acute and chronic cocaine influences the stimulus coding properties of individual sensory neurons, but will also provide a foundation for understanding how sensory circuits and networks would perform after cocaine is self-administered. As such these studies will establish a much needed link between the cellular actions of cocaine and behavioral data which suggest prominent short- and long-term effects of the drug on sensory systems and perceptual processes.