It is proposed to conduct investigations to utilize and further characterize newly developed genetic lines of mice which have been selectively-bred for either increased or decreased handling- induced convulsions (HIC) following withdrawal from ethanol (WSP and WSR lines). It is planned to determine if these genetically- based differences in susceptibility to HIC associated with physical dependence on ethanol are genetically related to susceptibility (cross-susceptibility) to HIC and other withdrawal signs associated with physical dependence on benzodiazepines, barbiturates, acetaldehyde, anesthetic gases, t-butanol, and several other sedative-hypnotic drugs. If so, then this would suggest that the mechanisms responsible for the intensity of HIC following ethanol withdrawal are also operative with these other drugs and/or withdrawal signs. Conversely, if ethanol HIC susceptibility does not generalize to these other drugs and/or withdrawal signs monitored, then independent controlling mechanisms are implicated. The development of these selected lines allows a novel approach to be utilized to determine the degree of commonality that exists among a number of drug dependencies with respect to alcohol. Additional studies are proposed to assess the role of the GABA and benzodiazepine receptors in the genesis of the alcohol withdrawal syndrome, utilizing in vitro receptor binding and receptor autoradiography in the WSP, WSR mice. The latter technique in particular will allow the detection of very small changes in receptor density caused by chronic intoxication and subsequent withdrawal from ethanol.
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