Effect of chemically induced propionic acidemia on neurobehavioral development of rats

High levels of propionic acid (PPA) comparable to those of human propionic acidemia were achieved in blood (1-5 mmol/l) and brain (1 mu mol/g) of rats by administering saline-buffered propionate (pH 7.4) subcutaneously twice a day from the 6th to the 28th day of life. PPA doses ranged from 1.44 to 1 .92 mu mol/g body weight as a function of animal age. Control rats were tre ated with saline in the same volumes. Growth and development of physical la ndmarks were assessed by monitoring the following parameters daily: body we ight, upper incisor eruption, eye opening, and hair coat. Development of so me reflexes was also monitored, and a specific subset of motor skills was e valuated at days 14 and 21 of life by the free-fall righting test and the s pontaneous alternation test. Chronic PPA administration had no effect on bo dy weight, cerebral cortex weight, or cerebellum weight, but caused slight but significant delays in the day of appearance of hair coat and eye openin g, indicating an effect of PPA on the development of physical parameters. F ree-fall righting was impaired in PPA-treated animals. On the other hand, P PA administration had no effect on the performance of the animals in the sp ontaneous alternation tests. Long-term effects of early PPA administration were investigated by assessing animal performance in an aversive task (two- way shuttle avoidance task) and in a nonaversive (open-field task) behavior al task at 60 days of age. PPA-treated rats did not habituate to the open f ield, and presented a lack of retention of the shuttle-avoidance task. Our results suggest that early postnatal PPA administration to rats alters norm al development and induces long-term behavioral deficits in aversive and no naversive tasks. (C) 1999 Elsevier Science Inc.