Modeling binge-like ethanol drinking by peri-adolescent and adult P rats

Abstract

Alcohol binge-drinking, especially among adolescents and young adults, is a serious public health concern. The present study examined ethanol binge-like drinking by peri-adolescent [postnatal days (PNDs 30-72)] and adult (PNDs 90-132) alcohol-preferring (P) rats with a drinking-in-the-dark-multiple-scheduled-access (DID-MSA) procedure used by our laboratory. Male and female P rats were provided concurrent access to 15% and 30% ethanol for three 1-h sessions across the dark cycle 5 days/week. For the 1st week, adolescent and adult female P rats consumed 3.4 and 1.6g/kg of ethanol, respectively, during the 1st hour of access, whereas for male rats the values were 3.5 and 1.1g/kg of ethanol, respectively. Adult intakes increased to ~2.0 g/kg/h and adolescent intakes decreased to ~2.5 g/kg/h across the 6 weeks of ethanol access. The daily ethanol intake of adult DID-MSA rats approximated or modestly exceeded that seen in continuous access (CA) rats or the selection criterion for P rats (≥5 g/kg/day). However, in general, the daily ethanol intake of DID-MSA peri-adolescent rats significantly exceeded that of their CA counterparts. BELs were assessed at 15-min intervals across the 3rd hour of access during the 4th week. Ethanol intake was 1.7 g/kg vs. 2.7 g/kg and BELs were 57 mg% vs. 100mg% at 15- and 60-min, respectively. Intoxication induced by DID-MSA in female P rats was assessed during the 1st vs. 4th week of ethanol access. Level of impairment did not differ between the 2 weeks (106 vs. 97 s latency to fall, 120 s criterion) and was significant (vs. naïve controls) only during the 4th week. Overall, these findings support the use of the DID-MSA procedure in rats, and underscore the presence of age- and sex-dependent effects mediating ethanol binge-like drinking in P rats.

Figure 1

Daily ethanol intake (mean ± SEM), averaged across 5-day blocks, by peri-adolescent female and male (top panel) and adult female and male (bottom panel) alcohol-preferring P rats given either continuous or binge-like (DID-MSA) concurrent access to 15% and 30% ethanol for 6 weeks. In general, peri-adolescent rats drank more ethanol than adult rats, female rats drank more ethanol than male rats, and adult female and male P rats increased, whereas peri-adolescent male P rats decreased, their ethanol intake across weeks. In addition, whereas peri-adolescent P rats given binge-like access generally consumed more ethanol than their continuous access counterparts, the pattern displayed by adult P rats was reversed with continuous access animals generally consuming more ethanol than their binge-like access counterparts. #, indicates a significant simple main effect of sex-of-animal for the respective 5-day block. *, indicates a significant simple main effect of ethanol condition for the respective sex-of-animal and 5-day block. $, indicates a significant change in ethanol intake between the 1^st and 6^th five-day blocks.

Figure 2

Results from the studies examining intoxication in adult (Experiment 3a, upper left and right panels as well as the lower left panel) or peri-adolescent (Experiment 3b, lower right panel) female alcohol-preferring P rats experiencing binge-like ethanol access (DID-MSA, with 15% and 30% available concurrently). Intoxication was assessed using an oscillating bar task, with latency to fall (sec) as the dependent variable (120 sec criterion). Experiment 3a assessed latency to fall (upper left panel), ethanol intake (upper right panel) and BELs achieved (lower left panel) during the 1^st (n = 11) vs. 4^th (n = 24) weeks of binge-like ethanol access. In general, significant intoxication was present only during the 4^th week of ethanol access, although the latency to fall did not differ between the rats tested during the 1^st week and the rats tested during the 4^th week of ethanol access. *, indicates a significantly lower latency (mean ± SEM) to fall by the ethanol-drinking compared with the ethanol-naïve rats, during the 4^th week of ethanol access. **, indicates a significance difference between the values for ethanol intake for the hr before the test for intoxication (upper right panel) and BELs (mean ± SEM) measured immediately after the test for intoxication (lower left panel) between that seen during the 1^st week of ethanol access and that seen during the 4^th week of ethanol access. Note that, for the peri-adolescent female P rats tested during the 4^th week of ethanol access (ethanol-drinking: n = 8, ethanol-naïve: n = 9), average ethanol intake prior to the test for intoxication was 2.9 ± 0.3 g/kg and average BELs achieved were 88 ± 14 mg% (mean ± SEM).