ALCOHOL PREDISPOSITION: COMPARATIVE WITHDRAWL SYNDROMES

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.