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 ethanol'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 between 36-96 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 postinjection intervals, in Experiment 1, did not produce any chromatogram peaks for ETOH or any its active metabolite (acetaldehyde, acetone, nor methanol).(ABSTRACT TRUNCATED AT 250 WORDS)
Gauvin
D V
DV
Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City 73190-3000.
Goulden
K L
KL
Holloway
F A
FA
D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001245:Association Learning / Q000187:drug effects* / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000097:blood / Q000139:chemically induced; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000523:psychology*
D000431:Ethanol; D002707:Chlordiazepoxide; D010433:Pentylenetetrazole