The subjective experiences resulting from acute high doses of ethanol have been termed """"""""hangover"""""""" in humans. The hangover effects, or the """"""""ethanol delayed effects"""""""" (EDE) may reflect a subjective precursor of withdrawal illnesses demonstrated after chronic ethanol exposure and may be regarded as a miniature model of the ethanol withdrawal syndrome. The present proposal would extend the analysis of the EDE to three physiological measures across a longer time frame than previously reported and to both acute and chronic ethanol dosing regimens. Using a remote radio telemetry computer-based system, electroencephalographic activity, core body temperature, and gross motor activity will be monitored in 50 male Sprague-Dawley rats. High dose pretreatments of ethanol (1.0, 2.0, 3.0, and 4.0 g/kg) will be administered and recordings will be taken for 48 hours post-treatment. A one-week """"""""wash out"""""""" period will be instituted between treatments. Two routes of administration (i.p. injections and ethanol inhalation) will be used for chronic ethanol dosing. The three physiological measures will be assessed during and for 120 hours after chronic treatments. Direct comparisons will be made between the EDE (rebound) and the chronic ethanol withdrawal syndrome in the same subjects. Multiple regression analysis and ANCOVA will attempt to dissociate whether the EDE and the ethanol withdrawal syndrome differ on a quantitative, qualitative, and/or temporal dimension. Assessment of the subjective effects of the acute ethanol exposure and resulting EDE (rebound) will be achieved by a two-choice drug discrimination task using pentylenetetrazol and saline in 12 male Sprague-Dawley rats. Test sessions will be conducted at various time points after 7 acute high dose pretreatments of ethanol. Two dependent measures (percentage of drug-appropriate responding, and rate of responding throughout the 10-minute experimental session) will be used. Two performance measures (schedule-controlled behavior) will also be used to measure the EDE in two groups of rats (n=12/group). Rats will be trained in either an FR-30 or DRL- 20 schedule operant task for food reinforcement. Once stable baseline performance is achieved, test sessions will be conducted at various time-points after acute high dose pretreatments of ethanol (from 15 minutes to 48 hours postinjection). The role of the acute physiological compensatory responses elicited by high doses of ethanol, their subjective and performance reduction effects, and their relationship to the chronic ethanol withdrawal syndrome may help to elucidate the functional role they may play in the development of tolerance and dependence.
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