Effects of short deprivation and re-exposure intervals on the ethanol drinking behavior of selectively bred high alcohol-consuming rats

Abstract

Alcoholics generally display cycles of excessive ethanol intake, abstinence and relapse behavior. Using an animal model of relapse-like drinking, the alcohol deprivation effect (ADE), our laboratory has shown that repeated 2-week cycles of ethanol deprivation and re-exposure, following an initial 6-week access period, result in a robust ADE by alcohol-preferring (P) and high alcohol-drinking (HAD-1 and HAD-2) rats. These rat lines have been selectively bred to prefer a 10% ethanol solution over water. The present study examined whether P and HAD rats would display an ADE using much shorter ethanol deprivation and re-exposure intervals. Rats were given either continuous or periodic concurrent access to multiple concentrations (10%, 20%, and 30% [vol/vol]) of ethanol. The periodic protocol involved access to ethanol for 12 days followed by four cycles of 4 days of deprivation and 4 days of re-exposure to ethanol access. High-alcohol-drinking rats displayed a robust 24-h ADE upon first re-exposure (HAD-1: approximately 5 vs. 8g/kg/day; HAD-2: approximately 6 vs. 9g/kg/day, baseline vs. re-exposure), whereas P rats ( approximately 7 vs. 8g/kg/day) displayed a modest, nonsignificant, increase in 24-h intake. In a separate group of rats, ethanol intake and blood alcohol concentrations after the first hour of the fourth re-exposure cycle were HAD-1: 2.0g/kg and 97 mg%, HAD-2: 2.3g/kg and 73 mg%, and P: 1.2g/kg and 71 mg%; with all three lines displaying a robust first hour ADE. These findings suggest that (a) an ADE may be observed with short ethanol deprivation and re-exposure intervals in HAD rats, and (b) the genetic make-up of the P and HAD rats influences the expression of this ADE.

Fig. 1

Effects of line [high-alcohol-drinking (HAD)-1 (n = 18, top panel) vs. HAD-2 (n = 20, middle panel) vs. P (n = 19, bottom panel)], sex-of-animal [male (n = 28) vs. female (n = 29)] and ethanol condition [continuous access (n = 61) vs. repeatedly deprived (n = 57)] on the expression of an alcohol deprivation effect [(ADE), ethanol intake as g/kg/day, mean (± S.E.M.)]. Baseline refers to the average of the last 4 days before the 1^st deprivation. #, indicates the presence of an ADE [significant (P < 0.025) increase in ethanol intake] after collapsing across sex of the respective line during the respective re-exposure block. Note: ethanol intake during the first 4-day block did not differ from that displayed during the baseline block for any of the lines. Similarly, ethanol intake during the last 4-day block did not differ from that displayed during the fourth re-exposure block for any of the lines. Overall, the findings indicate that, whereas HAD rats displayed a robust 24-hr ADE, P rats did not when using the present shortened protocol.

Fig. 2

Effects of line [high-alcohol-drinking (HAD)-1 (n = 39, top panel) vs. HAD-2 (n = 40, middle panel) vs. P (n = 39, bottom panel)], sex-of-animal [male (n = 58 vs. female (n = 60)] and ethanol condition [continuous access (n = 61) vs. repeatedly deprived (n = 57)] on water intake [ml/kg/day, mean (± S.E.M.)] averaged across 4-day blocks. For ease of presentation, symbols are absent. Overall, HAD-1 rats drank more water than P rats, which, in turn, drank more water than HAD-2 rats. Female rats drank more water than male rats, and, overall, repeatedly deprived animals drank more water than continuous access animals. Note that, in general, both male and female deprived P, and to a lesser extent male deprived HAD-2, rats displayed pronounced 31 increases in water intake during the ethanol deprivation cycles, whereas male and female deprived HAD-1 and female deprived HAD-2 rats did not display significant increases in water intake during the ethanol deprivation cycles. The vertical dotted lines indicate the 4-day blocks during which ethanol was withheld from the repeatedly deprived rats.

Fig. 3

Effects of line [high-alcohol-drinking (HAD)-1 (n = 39, top panel) vs. HAD-2 (n = 40, middle panel) vs. P (n = 39, bottom panel)], sex-of-animal [male (n = 58 vs. female (n = 60)] and ethanol condition [continuous access (n = 61) vs. repeatedly deprived access (n = 57)] on total fluid intake [ml/kg/day, mean (±S.E.M.)] averaged across 4-day blocks. For ease of presentation, symbols are absent. Overall, HAD-1 rats consumed slightly more fluids than P rats, which, in turn, drank more fluids than HAD-2 rats. Female rats drank more fluids than male rats, and, in general, repeatedly deprived animals drank more fluids than continuous access animals. The findings for the total fluid intake were, for the most part, opposite to those depicted for water intake in Fig. 2, such that male and female deprived P and, to some degree, male deprived HAD-2 rats displayed modest, if any, changes in total fluid intake across the 4-day blocks; whereas male and female deprived HAD-1 and female deprived HAD-2 rats displayed dramatic decreases in total fluid intake during the ethanol deprivation intervals. The vertical dotted lines indicate the 4-day blocks during which ethanol was withheld from the repeatedly deprived rats.

Fig. 4

Effects of line [high-alcohol-drinking (HAD)-1 (n = 39, top panel) vs. HAD-2 (n = 40, middle panel) vs. P (n = 39, bottom panel)], sex-of-animal [male (n = 58 vs. female (n = 60)] and ethanol condition [continuous access (n = 61) vs. periodic access (n = 57)] on body weight [g, mean (± S.E.M.)] averaged across 4-day blocks. For ease of presentation, symbols are absent. In general, P rats weighed more than HAD rats, male rats weighed more than female rats, and, except for differences between the repeatedly deprived and continuous access male HAD rats, there were no differences between ethanol condition. Because of the differences noted, all individual intake measures (daily ethanol, water, and total fluids) were corrected for the animals’ respective body weight.