Age Differences in the Expression of Acute and Chronic Tolerance to Ethanol in Male and Female Rats

Abstract

Background Ontogenetic differences in response to ethanol challenge have been observed under a variety of circumstances, including varying reports of developmental differences in the expression of tolerance to ethanol. The purpose of the present experiment was to further explore potential differences in acute and chronic tolerance expression between adolescent and adult, male and female Sprague-Dawley rats, using the social interaction test. Methods Acute (AT) and chronic (CT) tolerance to the social suppressing effects of a moderate dose of ethanol was assessed in adolescent and adult rats following i.p. injections of 2.0 g/kg EtOH or saline daily for 10 days. At test, adults and adolescents were challenged with 1.0 or 1.25 g/kg EtOH, respectively, with AT and CT assessed at 5 and 25 min post-injection using ratios of impairment to brain ethanol levels (BrECs) at each time period (CT) and within-session declines in impairment relative to BrECs (AT). Results In adolescents, 10 days of ethanol pre-exposure resulted in evidence of chronic tolerance at 25 min post-injection, perhaps associated with an enhanced expression of acute tolerance. Among adults, signs of chronic tolerance were seen at 5 min post-injection in adults, and may reflect neuroadaptations unassociated with acute tolerance, as with evidence of tolerance emerging only in adult control animals repeatedly exposed to saline injection prior to ethanol challenge on test day. Sex differences in tolerance expression were not observed at either age. Conclusions Our results show ontogenetic differences between adolescents and adults in the short and long-term neuroadaptations that they express in response to repeated perturbations with ethanol. Together these findings add age of exposure and time of testing within the intoxication period as critical variables to be considered when exploring the complex relationship between acute and chronic tolerance.

Sex, strain, and estrous cycle influences on alcohol drinking in rats

“…Although Robinson et al (2002) reported that the levels of alcohol peaked slightly faster in the blood and brain in females ( i.e ., faster absorption and distribution) and that alcohol elimination was slightly faster in female rats than in male rats, the effects were small and not sufficient to account for the large difference in female versus male drinking that was observed in the present study and in the literature. Additionally, Morales et al (2011) reported that male and female Sprague-Dawley rats exhibited similar levels of acute and chronic tolerance to the social suppressing effects of alcohol, thus supporting the hypothesis that sex differences in alcohol drinking observed in the present study were unrelated to tolerance to alcohol. For operant alcohol self-administration, we did not observe sex differences, consistent with some previous studies (van Haaren and Anderson, 1994; Moore and Lynch, 2015), although Blanchard et al (1993) reported that females self-administered more alcohol (10%, w/v) in a fixed ratio 3 schedule of reinforcement compared with males.…”

The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

“…Whereas previous studies examining social interactions utilized a 1-day test procedure (Morales et al 2011; Varlinskaya and Spear 2002), a 2-day test procedure that allows each experimental animal to serve as its own control was examined and validated in experiment 1 and used in the subsequent experiments. Using this procedure, each animal received vehicle on baseline and drug challenge on test day, thereby serving as its own control.…”

Sex differences in adult Wistar rats in the voluntary consumption of ethanol after pre-exposure to ethanol-induced flavor avoidance learning

“…Both sexes were included given that, despite evidence for sex differences in ethanol consumption (Blanchard et al, 1993;Doremus et al, 2005;Lancaster et al, 1996), relatively few studies have examined potential sex differences in the emergence of tolerance or sensitization to ethanol, and among those that have, the findings are mixed (Caihol and Mormede, 2002;Linsenbardt et al, 2009;Morales et al, 2011;Sherrill et al, 2011a;Webb et al, 2002). In fact, the conditions under which the stimulus properties of ethanol change with repeated exposure are not well defined, especially with regard to differences in male vs female responses to repeated exposure to ethanol.…”