Sex differences in vulnerability to developmental spatial learning deficits induced by limited binge alcohol exposure...

The two main objectives of this study were (1) to replicate previous findings that 6 days of binge-like exposure to alcohol during the neonatal brain growth spurt induces significant place learning deficits in juvenile rats and (2) to determine whether more limited (3-day) binge-like exposure during the neonatal period induces place learning deficits and whether the effects depend on the developmental timing of the exposure. Using artificial rearing methods and a split-litter experimental design, groups of male and female neonatal rats were given binge-like exposure to 4.5 g/kg/day of ethanol in milk formula either on Postnatal Days (PD) 4-6, PD 7-9, or PD 4-9, which yielded mean peak blood alcohol concentrations of 230-260 mg/dl. Controls included an artificially reared gastrostomy control group (GC) given an isocaloric milk formula diet on PD 4-9 and a suckle control group reared normally by lactating dams. Acquisition of place learning in the Morris spatial navigation task was trained for 6 consecutive days beginning on PD 26; a probe trial was given at the end of the sixth day. As expected, both males and females given alcohol on PD 4-9 had significant deficits in acquisition and probe trial performance relative to SC and GC groups. Males given the PD 7-9 exposure had significant place learning deficits which were as severe as with the full 6-day exposure. The PD 4-6 exposure in males produced only a nonsignificant trend toward slower acquisition. Females were not significantly affected by either 3-day exposure. The latter phase of the neonatal brain growth spurt appears to constitute a sex-specific period of enhanced vulnerability to alcohol-induced developmental spatial learning deficits.