Characterizing the interoceptive effects of ethanol in adolescent and adult rats using a Pavlovian discrimination procedure

Although adolescents and adults vary in sensitivity to various effects of ethanol, no previous studies have assessed age differences in the interoceptive (i.e., subjective) effects of ethanol as indexed via ethanol discrimination. This dissertation examined potential age differences in ethanol discrimination using a Pavlovian occasion setting discrimination model that generates discrimination scores based on approach behavior during ethanol and saline sessions. Chapter 1 examined acquisition and dose-response generalization in isolate-housed, food-restricted adolescent and adult rats following various training parameters, including multiple ethanol training doses (0.75, 1.0, and 1.25 g/kg, i.p.) at different time points (5 or 30 min pre-session). Ethanol served as either a positive or negative occasion setter for each subject. Adults had higher discrimination scores during acquisition and broader ethanol generalization during test sessions than adolescents. The 1.0 g/kg ethanol training dose proved optimal for comparing adolescents and adults and was used in subsequent studies. In order to determine whether Chapter 1 findings were a result of isolate housing, Chapter 2 compared acquisition and dose response generalization in isolate and pair-housed adolescents and adults. No housing effects were seen with either measure. Chapter 3 explored potential age differences in neural substrates contributing to ethanol's interoceptive effects. In adults, NMDA antagonists and GABAA agonists are consistently reported to substitute for ethanol, and subunits of these receptors have been shown to undergo ontogenetic alterations. Thus, following discrimination acquisition, four subunit-selective compounds were tested for ethanol substitution (PEAQX: GluNR2A; ifenprodil: GluNR2B; L838,417: GABAA &agr;2/&agr; 3/&agr;5; THIP: GABAA &agr;4/&agr; 6/delta). Tissue from discrimination-trained and ethanol-naive animals was also collected to assess receptor subunit expression using Western blotting techniques. None of the compounds substituted for adolescents. PEAQX was the only compound to partially substitute for ethanol in adult rats. Although age and discrimination training influenced subunit expression in some brain regions, no changes were seen with the GluNR2A subunit. Results from the present studies suggest that ethanol is a more salient cue for adults than adolescents. Further, although age-typical ethanol insensitivity may compromise interpretation of adolescent substitution data, the adult data are the first to suggest involvement of GluNR2A-containing receptors in ethanol's interoceptive effects.