State-dependent stimulus control: cueing attributes of ethanol "hangover" in rats.

In Experiment 1, twelve 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 ethan-ol's (ETOH) delayed or rebound effects (EDE) versus “normal” basal homeostasis. Rats were injected with either 4 g/kg ETOH or equivalent volumes of saline (SAL) 18 hr before the sessions. Each rat was injected with an additional 1 ml/kg injection of SAL 15 min before the sessions. EDE training sessions were always followed by a “day off.” SAL sessions were conducted between36–96 hr after an EDE training session. Rats demonstrated>90% discriminative accuracy. Test sessions showed a time-dependent, cyclic, return from the experimental “hangover” state to the “normal” state, by 48 hr. The acute (immediate) effects of ETOH and chlordiazepoxide (0.75 g/kg or 0.18 mg/kg, respectively; 15 min) did not cross-generalize with the “hangover” state. Both these low-dose ETOH and chlordiazepoxide pretreatments blocked the stimulus attributes of “hangover.” All subjects responded on the EDE-appropriate lever at 5.6 mg/kg pentylenetetrazole and exhibited an increase in susceptibility to clonic seizures. In Experiment 2 blood alcohol concentration kinetics functions were quantified in three groups (n = 8/ group) of age-matched cohorts to Experiment 1 subjects (2, 3, and 4 g/kg ETOH) using a head-space gas chromatographic technique. The training stimulus state associated with 4 g/kg, at 18 hr postin-jection intervals, in Experiment 1, did not produce any chromatogram peaks for ETOH or any its active metabolite (acetaldehyde, acetone, nor methanol). The present data demonstrated the saliency and “anxiogenic” dimensionality of experimentally induced “hangover.”