PERINATAL METHANOL EXPOSURE IN THE RAT .2. BEHAVIORAL-EFFECTS IN NEONATES AND ADULTS

The use of methanol as a component of automobile fuel will increase pe rinatal exposures in the general population. Few studies have addresse d questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each coho rt consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr dai ly beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonat al toxicity in humans. Several behavioral procedures were used to asse ss exposure effects in the offspring. Male-female littermates were stu died whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckl ing latency and nipple attachment on PND 5 or performance on an aversi ve olfactory conditioning procedure on PND 10. Exposure to methanol di d alter performances in a motor activity procedure. Methanol-exposed n eonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, n ot used previously in this context, assayed other littermates as adult s. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. Wh en the fixed ratio requirement changed, number of responses (revolutio ns) per 1-hr session displayed a complex interaction with treatment. C hanges in performance over the course of training differed between mal es and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and me thanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determin ed by the location of the preceding response. A reinforcement matrix d efined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was asso ciated with subtle behavioral changes in both neonates and adults. (C) 1997 Saciety of Toxicology.