This pilot project examines the role of prefrontal cortex in alcohol- seeking behavior and alcohol consumption in the non-human primate. The project exploits our knowledge of prefrontal anatomy, physiology and pharmacology to explore D1 and D2 receptor modulation of alcohol- induced changes in neural responses associated with working memory performance in trained non-human primates. We will use single neuron recording combined with iontophoretic drug application in monkeys trained to perform a visuospatial memory task to unravel the cortical cellular involvement of prefrontal circuits in addictive behavior. Using this methodology, we are able to dissociate sensory, mnemonic and motor related neural processes and correlate cellular events with these components of behavioral function. The three aims of this proposal are (1) the examination of cue, delay and response-related neuronal response in prefrontal cortex to cues associated with alcohol reward; (2) analysis of the role of cortical post-synaptic D1 and D2 receptors in supporting or antagonizing these alcohol-engendered responses; and (3) to chart the dynamic shifts in neuronal responses an dopamine modulation of these responses during, and after cessation of chronic alcohol administration as well as correlate these changes with trends in behavior performance. These findings are expected to provide insight into the presently obscure cortical mechanisms relevant to alcohol addiction and explore the relationship between cognitive performance and addictive behavior.
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