Ontogeny of Acute Tolerance to Ethanol‐Induced Social Inhibition in Sprague–Dawley Rats

Abstract

Background: Adolescent rats are less sensitive than adults to a number of acute effects of ethanol, including ethanol‐induced social inhibition. Adolescent insensitivity to the suppressing effects of ethanol on social interactions could be related in part to age differences in compensatory responses, including acute tolerance, that serve to counteract these inhibitory effects of ethanol. The present study explored ontogenetic development of acute tolerance within 30 minutes after administration of a relatively low ethanol dose, using ethanol‐induced social impairment as the target response measure. Methods: Overall social activity was examined following challenge with 1 g/kg ethanol (intraperitoneally) at 2 postinjection intervals (5 or 30 minutes) in early [postnatal day (P) 28], mid (P35), or late (P42) adolescent or adult (P70) group‐housed male and female Sprague–Dawley rats (Experiment 1). Blood and brain ethanol concentrations (BECs and BrECs) were assessed in separate groups of animals 5 or 30 minutes after ethanol administration (Experiment 2). Expression of acute tolerance was examined by assessing the relationship between BrECs and the degree of social impairment in individual animals at P28, P35, P42, and P70 during early recovery period (up to 30 minutes) following acute ethanol challenge (Experiment 3). Results: Effects of ethanol on overall social activity were age‐dependent and time‐dependent. Whereas all age groups showed equivalent ethanol‐induced social inhibition 5 minutes after injection, testing at 30 minutes revealed marked age differences. Social inhibition was still pronounced at this time in adults, but was diminished in an age‐related manner at younger ages (Experiment 1). In contrast to the ontogenetic differences in rates of decline in social impairment across time, decreases in brain and blood ethanol levels over time were similar across age (Experiment 2). Only P28 and P35 adolescents showed acute tolerance to ethanol‐induced social inhibition, as indexed by an increasing time‐dependent dissociation between BrECs and ethanol‐induced social impairment, with social impairment declining faster than BrECs (Experiment 3). Conclusions: This is the first study to document enhanced acute tolerance in adolescent rats relative to adult animals at nonhypnotic doses of ethanol. The greater expression of acute tolerance in young animals may reflect an enhanced predisposition of their nervous systems to respond rapidly to even modest doses of ethanol with compensatory adaptations. A greater propensity of early adolescents to develop acute tolerance may contribute to their resistance to adverse effects of ethanol, thereby permitting heavy drinking at this age and placing early adolescents at higher risk for extensive alcohol use.