Temporal determinants of neonatal alcohol-induced cerebellar damage and motor performance deficits.

The timing and duration of alcohol exposure was manipulated in neonatal rats by using a "binge" model of alcohol exposure during the "third trimester equivalent." Groups of Sprague-Dawley rats were exposed to binges via artificial rearing on postnatal days (PD) 4-9, on PD 4-6 or on PD 7-9, which produced peak blood alcohol concentrations representative of human alcohol abusers (approximately 250 mg/dl). Motor performance was assessed using parallel bar traversal on PD 42-44, and total Purkinje cell numbers were determined by using the 3-dimensional stereological optical fractionator method. PD 4-9 binge exposure induced the most severe Purkinje cell loss (to 68% of controls) and PD 4-6 binge exposure also produced significant loss (to 86% of controls), whereas PD 7-9 binge exposure had no significant effect (98% of controls). Unexpectedly, all three alcohol treatments resulted in significant impairments on the parallel bar task. The time of exposure during the early neonatal period in rats strongly influences the degree of Purkinje cell loss, but Purkinje cell loss is not necessary for the alcohol-induced motor performance deficits. Both neuromorphological and neurobehavioral assessments are needed for a full description of alcohol-related neurodevelopmental disorders.