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.