CORRELATED RESPONSES TO SELECTION IN FAST AND SLOW MICE - EFFECTS OF ETHANOL ON ATAXIA, TEMPERATURE, SEDATION, AND WITHDRAWAL

A replicated bidirectional selective breeding program has produced lin es of mice that differ in locomotor response to ethanol (EtOH). FAST m ice were bred for high locomotor activation, whereas SLOW mice were br ed for low or depressed locomotor activity in response to 2.0 g/kg of EtOH. We tested FAST and SLOW mice for differences in sensitivity to t he incoordinating (1.5 to 2.5 g/kg), hypothermic (3.0 g/kg), and sedat ive (4.0 g/kg) effects of EtOH, and for differences in sensitivity to withdrawal after acute and chronic EtOH exposure. SLOW mice were more ataxic in a grid test and developed greater tolerance than FAST mice a t 2.0 g/kg of EtOH, were more hypothermic than FAST mice, and were mor e sensitive to the sedative effects of EtOH than FAST mice, as measure d by latency to and duration of loss of righting reflex, and by blood ethanol concentrations at regain of the righting reflex. FAST mice had more severe withdrawal seizures after chronic exposure, but did not d iffer from SLOW mice in withdrawal severity after an acute injection o f EtOH. These data suggest that FAST mice are generally more sensitive to central nervous system excitation, and SLOW mice are generally mor e sensitive to central nervous system sedation by EtOH, and further su ggest genetic overlap with respect to genes that mediate locomotor res ponses to EtOH and genes determining sensitivity to EtOH-induced ataxi a, hypothermia, sedation, and withdrawal severity after chronic exposu re. Our current observations are in contrast to observations made earl ier in selection, in which few line differences in sensitivity to EtOH effects other than locomotor activity were found. Thus, it seems that continued selection for differences in locomotor response to EtOH has produced genetically correlated differences in other EtOH responses.