Dose-dependent deficits in dual interstimulus interval classical eyeblink conditioning tasks following neonatal binge alcohol exposure in rats

Background: Neonatal alcohol consumption in rats is widely used to model cerebellar injury arising from 3rd-trimester human fetal alcohol exposure. Binge alcohol exposure of 5 g/kg/day or more over postnatal days (PD) 4 to 9 in rats damages the cerebellum and consequently impairs classical eyeblink conditioning (EBC). The present study sought to identify deficits in EBC using doses lower than those that have been reported previously following alcohol exposure limited to PD4-9. Complex conditioned response (CR) timing tasks utilizing 2 interstimulus intervals (ISIs) were used to test the hypothesis that 3 g/kg/day of alcohol would produce early onset and early peaked CRs, whereas 4 and 5 g/kg/day would impair CR acquisition. Methods: Five neonatal treatment groups were used: (1) undisturbed controls, (2) sham intubation controls, (3) 3 g/kg/day of alcohol, (4) 4 g/kg/day of alcohol, or (5) 5 g/kg/day of alcohol. Intubations occurred over PD4-9. In adulthood, rats were trained using ISI discrimination (Experiment 1) or temporal uncertainty (Experiment 2) EBC tasks. In ISI discrimination, 2 distinct conditioned stimuli (CSs; tone and light) are reinforced with a periocular shock unconditioned stimulus (US) at 2 different CS-US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both CS-US intervals. Results: Alcohol-exposed subjects were impaired in CR acquisition in a task- and dose-dependent fashion. CR deficits were most salient in the peak amplitude measure and occurred in both tasks following alcohol exposure at 4 and 5 g/kg/day. Alcohol at a dosage of 3 g/kg/day impaired CR acquisition only in ISI discrimination. All alcohol doses failed to produce short latency CRs in either task. Alcohol-exposed subjects displayed later-onset and later-peaked CRs to the long-ISI CS in ISI discrimination relative to controls. Conclusions: ISI discrimination training may be ideal to identify CR deficits resulting from neonatal exposure to moderate alcohol doses. Applications of this EBC task to humans may enable reliable early identification and diagnosis of individuals with fetal alcohol spectrum disorders.