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 lines of mice that differ in locomotor response to ethanol (EtOH). FAST mice were bred for high locomotor activation, whereas SLOW mice were bred for low or depressed locomotor activity in response to 2.0 g/kg of ETCH. We tested FAST and SLOW mice for differences in sensitivity to the incoordinating (1.5 to 2.5 g/kg), hypothermic (3.0 g/kg), and sedative (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 at 2.0 g/kg of EtOH, were more hypothermic than FAST mice, and were more sensitive to the sedative effects of EtOH than FAST mice, as measured 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 differ from SLOW mice in withdrawal severity after an acute injection of EtOH. These data suggest that FAST mice are generally more sensitive to central nervous system excitation, and SLOW mice are generally more sensitive to central nervous system sedation by EtOH, and further suggest genetic overlap with respect to genes that mediate locomotor responses to EtOH and genes determining sensitivity to EtOH-induced ataxia, hypothermia, sedation, and withdrawal severity after chronic exposure. Our current observations are in contrast to observations made earlier 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.