Cocaine is a euphorigenic drug that is subject to widespread abuse. 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 this proposal is how cocaine affects sensory neurons and sensory processing within a primary sensory cortex. Initial finding suggest that it will be necessary to obtain specific information concerning the influences of cocaine on individual cellular components of the cerebrocortical circuitry in order to fully comprehend the potential impact of this drug on the signal processing capabilities of a sensory cortical network. Thus, the hypothesis to be tested is that cocaine effects in the somatosensory cortex are related to specific neural attributes of membrane function, morphology, axonal projections and innervation by monoamine terminals. These experiments will be conducted using intracellular recording in the in vitro brain tissue slice preparation. Electrophysiological parameters of membrane function, transmitter-induced and evoked post-synaptic potentials, under cocaine and related substances will be recorded. Cell morphology and monoaminergic terminals will be visualized using immunohistochemical methods. In addition, 3 specific points will be addressed: 1) pre- versus post synaptic actions of cocaine; 2) interactions of cocaine with norepinephrine and serotonin systems and 3) pharmacological specificity of cocaine. The goal of this work is to redefine the actions of cocaine at membrane and synaptic levels in relation to morphology and monoaminergic inputs. These studies by characterizing subclasses of sensory neurons that are target for cocaine actions will 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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