Clinical studies indicate that prolonged ethanol abuse by alcoholics results in an increasing incidence of seizure susceptibility until the majority of alcoholics have this symptom. A kindling-like phenomenon produced by repetitive withdrawal from alcohol has been proposed to explain this observation. Recently, the inferior colliculus has been implicated in the genesis of audiogenic seizures following withdrawal from chronic ethanol. Since chronic electrical stimulation of the inferior collicus also produces a kindling-like phenomenon, we propose that, like repeated electrical stimulation, repeated withdrawal episodes from chronic ethanol """"""""kindles"""""""" the inferior colliculus or other sites. To test this hypothesis, we will determine if repeated withdrawal episodes from chronic ethanol exposure increases the sensitivity of the inferior colliculus to electrically elicited seizures after rats have recovered from the acute withdrawal. These results will be compared to studies of the amygdala, a classic site for kindling, as more than one site may be involved in the kindling process. Conversely, we will determine a chronic stimulation of the inferior colliculus or amygdala will increase seizure susceptibility of chronic ethanol-treated rats upon withdrawal. Since the inferior colliculus is a crucial component for audiogenic seizures in rats treated chronically with ethanol, the neural pathways involved in both the ethanol withdrawal seizures and electrically elicited seizures from the inferior colliculus will be mapped using site injection of local anesthetics. ln addition, pharmacological interventions are planned to determine if the seizure process induced by these treatments can be attenuated. An in vivo dialysis technique will be used to define the release of excitatory and inhibitors neuroactive amino acids in the inferior colliculus following acute or chronic ethanol treatment to allow a better understanding of the neurochemical changes induced be ethanol. Investigation will explore also the role of chloride channels in ethanol's actions and will compare the biochemical consequences of kindling with changes induced by repeated ethanol withdrawal. Electrophysiological investigations in the inferior colliculus will define changes in cell responsiveness of excitatory and inhibitory transmitters after acute or chronic ethanol. These multidisciplinary investigations should provide new information concerning the genesis of seizures induced by chronic ethanol consumption and allow us to examine the neurochemical basis for the acute actions of ethanol on CNS function as well as the associated adaptation with continued ethanol exposure.
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