Sex Differences in Vulnerability to Developmental Spatial Learning Deficits Induced by Limited Binge Alcohol Exposure in Neonatal Rats

Abstract

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 gastro- stomy 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.