Chronic Tolerance to Ethanol in the N:NIH Rat

As the basis for selectively breeding rats from the N:NIH stock on the basis of differential development of tolerance to ethanol, chronic tolerance to the motor‐disrupting effects of ethanol was examined. Male (n= 50) and female (n= 46) rats were administered 2.5 g/kg ethanol (i.p.) and the blood‐ethanol concentration (BEC) at the time of regain of aerial righting reflex (RARR) was measured. The rats were then placed in inhalation chambers for 8 consecutive days and chronically exposed to ethanol. Thirty‐two hours following the cessation of chronic ethanol exposure, the rats were again given a 2.5 g/kg dose of ethanol and the BEC at RARR was again measured. The amount of chronic ethanol tolerance developed, as measured by the difference in BEC at RARR prior to and after chronic ethanol administration, was widely and normally distributed for both male and female rats. Control rats, which did not receive chronic ethanol exposure between the two tests of RARR, did not show tolerance on this measure. A negative correlation (r= ‐0.46) was found between BEC at RARR prior to chronic ethanol treatment and the amount of chronic tolerance developed using the difference in BEC measure. This correlation suggested that the rats who were initially more sensitive to the effects of ethanol were more likely to display the greatest amount of chronic tolerance. However, using the residuals of the regression analysis of post‐chronic ethanol BEC at RARR on prechronic BEC at RARR as an index of tolerance, this negative correlation was not found. Thus, while the difference scores may be appropriate for chosing individuals to breed in a selection study, it appears that using a difference score to assess the development of tolerance could lead to an incorrect assessment of the relationship between initial sensitivity and tolerance.