Responsivity and development of tolerance to the motor impairing effects of moderate doses of ethanol in alcohol-preferring (P) and -nonpreferring (NP) rat lines

Background: Research comparing the alcohol-preferring (P) and -nonpreferrin g (NP) rat lines has detected an apparent association between ethanol prefe rence and lower responsivity to ethanol, as well as the capacity to develop and maintain tolerance to ethanol's effects However, past studies of toler ance to ethanol's effects generally involved relatively high doses. The pre sent study examined recovery from functional impairment induced by moderate doses of ethanol after a single dose (responsivity) and after multiple dos es (development of tolerance) in the P and NP rat lines. Method: Adult female P and NP rats were trained, for 5 consecutive days, to stay on an oscillating bar for 120 sec. Rats were then assigned to one of three groups to receive 1.0, 1.25, or 1.5 g/kg ethanol for 5 consecutive te st days. Rats were tested each day at 15-min intervals, following intraperi toneal injection, until recovery to the 120 sec criterion. Results: On the first test day, NP rats took longer to recover to criterion than the P rats following the 1.0 and 1.25 g/kg doses, whereas at the 1.5 g/kg dose no line difference was evident. Trunk blood alcohol concentration s (BACs), associated with time to recovery, indicated higher values fur the P than NP rat on day 1 following injection of the two lower doses. Compare d to day 1, NP rats demonstrated significantly shorter times to recovery be ginning on day 2 following injections of the 1.0 and 1.25 g/kg doses. Howev er, NP rats did not show significantly different recovery times on days 2-5 compared to day 1 following injection of the 1.5 g/kg dose. The shorter re covery times at the 1.0 and 1.25 g/kg doses were associated with BACs at re covery on day 3 being equal to or greater than values obtained on day I. In contrast, compared to day 1, P rats did not show shorter recovery times un til days 3 and 5 following the 1.0 and 1.25 g/kg doses, respectively. Howev er, P rats did demonstrate shorter recovery times on day 2 and higher BACs on day 3 compared to day 1 following the 1.5 g/kg dose. Conclusion: With regard to motor impairment, lower responsivity to moderate doses of ethanol may be a factor associated with high alcohol-seeking beha vior. The present results confirm past research supporting an association b etween ethanol preference and low ethanol responsivity but at doses that ar e more reflective of those self-administered by P rats.