Cross-generalization of an EtOH "hangover" cue to endogenously and exogenously induced stimuli.

Twenty male Sprague-Dawley rats were trained in a two-choice food-reinforced drug discrimination task (10 min sessions) using the state-dependent interoceptive stimulus attributes of ethanol's (EtOH) delayed or rebound effects (EDE) versus "normal" basal homeostasis. Cross-generalization tests were conducted with 0.18 mg/kg naloxone injected after three days of three injections per day of either SAL or 10 mg/kg morphine. Naloxone failed to generalize to the EDE-state after chronic saline; however, the precipitated morphine withdrawal state produced complete generalization to the EDE training cue. Daily tests were conducted after 8 h photoperiod phase-shifts. An 8 h phase-advance, equivalent to a west-to-east intercontinental night-time flight in humans, produced a biphasic, graded, increase in EDE-appropriate responding, which peaked on the second day after the phase-advance and recovered by the fourth day. The 8 h phase-delays failed to engender significant EDE-appropriate responding. These data provide evidence for the subjective similarity between EtOH hangover, opiate withdrawal states, and the physiological disruption induced by circadian phase-advances.

Cumulative vs. acute dose-response procedures produce differential BAC and behavioral functions for ethanol.

The discriminative stimulus attributes of ethanol (ETOH) were characterized in rats trained to discriminate between 1.25 g/kg ETOH and saline. The ETOH generalization functions were assessed using both acute and cumulative dosing procedures. The cumulative procedures differed in the individual incremented doses used to generate the functions. Acute dosing procedures produced discriminative functions that were significantly different from cumulative dose-response curves (DRCs). Similar cumulative DRC's were generated within each cumulative dosing procedure, whereas significant differences were produced between the two dosing incremented procedures. When blood alcohol concentrations (BACs) were quantified, a cumulative testing procedure produced significantly lower BACs than acute testing procedures at every dose above the initial or starting dose. Interestingly, response rate functions did not differ within or between cumulative and acute procedures. These data may suggest that differential ETOH dosing procedures may differentially influence the behavioral choice and BAC functions in rats, and cautions against the use of cumulative procedures to assess shifts in DRCs during chronic treatments without a concomitant assessment of BACs.