Acute, rapid, and chronic tolerance during ontogeny: Observations when equating ethanol perturbation across age

Background: Sensitivity to the motor-impairing and hypnotic effects of etha nol (EtOH) increases notably during development. Less is known, however, ab out the ontogeny of EtOH tolerance and the ontogenetic relationship among d ifferent types of tolerance. Consequently, we compared the ontogenetic deve lopment of acute, rapid, and chronic tolerance to EtOH-induced motor impair ment and hypothermia in a swim task. Methods: Preweanling, adolescent, and adult female and male Sprague-Dawley rats were given chronic saline (control group), five daily EtOH exposures b efore EtOH on test day (chronic group), one EtOH exposure before test day ( rapid group), or EtOH exposure only on test day (acute groups). Separate gr oups of animals in the acute groups were tested at 15, 60, or 105 min after injection to estimate acute tolerance development via calculating slopes o f the linear regression of impairment relative to brain alcohol levels at e ach postinjection interval. Initial EtOH perturbation of swim performance w as equated across age by varying EtOH dose. Results: Acute tolerance was evident to the motor-impairing effects of EtOH at all ages. When impairment was indexed relative to brain alcohol levels, rapid and chronic tolerance to the motor-impairing effects of EtOH on late ncy to reach the start was seen across age, although this tolerance tended to be more pronounced in adults. Somewhat different ontogenetic patterns of tolerance development were observed with EtOH-induced hypothermia, a depen dent measure for which EtOH perturbation was not equated across age. Conclusions: The degree of initial perturbation by EtOH seems to be an impo rtant predictor of tolerance expression during ontogeny. That is, ontogenet ic profiles of tolerance development differ significantly when EtOR-induced motor impairment is equated across age rather than dose of EtOH administer ed. The role of target response measures and context stress should also be considered when exploring ontogenetic expression of EtOH tolerance.