The relationship between genetic liability to alcohol tolerance and alcohol withdrawal has been evaluated in rodents in three ways (see ref. 45 for a detailed review). First, two pairs of mouse lines have been selectively bred to be sensitive to alcohol withdrawal, as measured by the emergence of mild or severe handling-induced convulsions after a period of chronic alcohol vapor inhalation.46 Despite a more than 10-fold difference in alcohol withdrawal severity in the withdrawal seizure-prone and -resistant selected lines, these lines do not differ in the magnitude of their ethanol tolerance, as assessed by chronic ethanol-induced hypothermia or by loss of righting reflex duration.47 Second, the correlation between mean strain values for alcohol tolerance and withdrawal severity has been assessed in a range of inbred mouse strains. Acute alcohol withdrawal severity48 did not correlate significantly across these inbred strains with the magnitude of tolerance to ethanol hypothermia49 or to the duration of loss of righting reflex.50 Third, 20–27 recombinant inbred strains created from the DBA/2J and C57BL/6J mouse strains have been examined for several phenotypes that reflect alcohol tolerance and
