STATE-DEPENDENT STIMULUS-CONTROL - CUEING ATTRIBUTES OF ETHANOL HANGOVER IN RATS

In Experiment 1, twelve Sprague-Dawley rats were trained in a two-choi ce food-reinforced drug discrimination task (10 min sessions) using th e state dependent interoceptive stimulus attributes of ethanol's (ETOH ) delayed or rebound effects (EDE) versus ''normal'' basal homeostasis . Rats were injected with either 4 g/kg ETCH 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 tr aining sessions were always followed by a ''day off.'' SAL sessions we re conducted between 36-96 hr after an EDE training session. Rats demo nstrated >90% discriminative accuracy. Test sessions showed a time-dep endent, cyclic, return from the experimental ''hangover'' state to the ''normal'' state, by 48 hr. The acute (immediate) effects of ETCH 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 ETCH and chlordiazepoxide pretreatments blocked the stimulus attribut es of ''hangover.'' All subjects responded on the EDE-appropriate leve r at 5.6 mg/kg pentylenetetrazole and exhibited an increase in suscept ibility to clonic seizures. In Experiment 2 blood alcohol concentratio n kinetics functions were quantified in three groups (n = 8/group) of age-matched cohorts to Experiment 1 subjects (2, 3, and 4 g/kg ETCH) u sing a head-space gas chromatographic technique. The training stimulus state associated with 4 g/kg, at is hr postinjection intervals, in Ex periment 1, did not produce any chromatogram peaks for ETCH or any its active metabolite (acetaldehyde, acetone, nor methanol). The present data demonstrated the saliency and ''anxiogenic'' dimensionality of ex perimentally induced ''hangover.''