The specific aims of the proposed series of studies are 1) to fully characterize the frequency, amplitude, and time course of EEG spectra following low """"""""intoxicating"""""""" doses (0.5-1.5 g/kg) of ethanol in monkeys 2) to determine what aspects or components (latency, amplitude, frequency, morphology) of monkey event related potentials (ERPs) are particularly susceptible to low (0.5-1.5 g/kg) doses of ethanol. 3) To test the hypothesis that some of the electrophysiological indices (EEG, ERPs) of low, """"""""intoxicating"""""""" doses of ethanol may be mediated by opioid peptides 4) to evaluate the potential interactions of the recently characterized hypothalamic peptides, corticotropin releasing factor (CRF) and growth hormone releasing factor (GRF) with low doses of ethanol. We will extend our preliminary results which suggest that low doses of ethanol dramatically alter the time course of monkey cortical EEG spectra as well as monkey homologues of human ERPs. In one series of experiments we plan to record and computer analyze EEG from subcortical and cortical sites in order to determine what brain sites are the most sensitive to low dose ethanol and the potential antagonism of its effects by naloxone. In a separate series ERPs will be obtained from cortical and subcortical sites from monkeys presented with 2 paradigms; an """"""""oddball"""""""" paradigm designed to obtain late positivites and secondly a series of clicks presented at high rates designed to obtain a 40 HZ ERP from the middle latency response. The effects of ethanol (0.5-1.5 g/kg) and ethanol plus naloxone will be tested in both ERP paradigms. We also have preliminary results in rats which show that the hypothalamic peptides CRF and GRF can produce potent changes in EEG and behavioral state; with CRF producing increased signs of arousal and GRF producing decreases. We plan to extend these studies to the squirrel monkey where we will test the interaction between low doses of ethanol and these peptides utilizing measurements of EEG, ERPs and behavioral observations. We believe these studies may identify clinically relevant encephalographic """"""""markers"""""""" of acute ethanol intoxication, which are relevant to humans. In addition the study of possible neurochemical variables which may underlie the individual differences in response to ethanol and which may lead to different drinking patterns may reveal what variables are antecedent to alcoholism or alcohol abuse.
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