Prenatal phenytoin exposure and spatial navigation in offspring: Effects on reference and working memory and on discrimination learning

Previous research has shown that rats exposed to phenytoin (PHT) in utero d emonstrate abnormal circling, decreased learning, hyperactivity, and delaye d air righting reflex development. The effects of prenatal PHT on offspring learning have been found on multiple-T mazes (Biel and Cincinnati types) a nd on spatial navigation (Morris maze). However, the specificity of the lat ter effects is unknown. Herein, we tested the effects of prenatal PHT in a Morris maze using six different procedures: cued versus spatial reference m emory-based learning, cued versus spatial working memory-based learning, an d cued versus spatial discrimination learning. PHT-exposed offspring showed increased preweaning mortality, growth reduction, and abnormal circling as noted in previous studies. PHT offspring were separated into those exhibit ing circling and those not. PHT noncircling offspring demonstrated impaired reference memory-based spatial learning (acquisition and reversal), but no other effects. By contrast, PHT circling offspring demonstrated not only i mpaired reference memory-based spatial learning, but also impaired cued pla tform learning, impaired spatial discrimination, and impaired working memor y-based learning. These data confirm that prenatal PHT induces a specific r eference memory-based spatial learning deficit even in asymptomatic (noncir cling) offspring that is distinct from the impairment induced in littermate s exhibiting the circling impairment. (C) 1999 Elsevier Science Inc. All ri ghts reserved.