AGE AND DOSE-RELATED EFFECTS OF HIPPOCAMPAL IBOTENIC ACID ON LESION SIZE, MORTALITY, AND NONSPATIAL WORKING-MEMORY IN INFANT RATS

Three experiments are presented in which the neural and behavioral con sequences of multiple ibotenic acid (IBO) injections into the hippocam pus were examined in Sprague-Dawley rat pups. Rat pups were 11 or 15 d ays of age at the time of surgery (SURG11, SURG15), the dose of IBO wa s either 1 mu g in 1 mu l, 2.5 mu g in 0.5 mu l, or 5 mu g in 1 mu l f or each of four injections, and pups were allowed to survive for 3 or 7 days after the lesion was made. The Fink-Heimer silver stain was use d in Experiment 1 to examine the extent of neural damage following uni lateral lesions and showed that the degeneration was primarily located in the hippocampus. The magnitude of the damage was greatest in young er pups and in those which received the higher of the two concentratio ns (injection volume was not a factor). Degenerating fibers were seen in the columns of the fornix as well as precommissural fornix fibers, but only in SURG15 animals when damage extended into the dorsal subicu lum. Mortality rates following multiple IBO injections were very high in infant rats, in some cases as high as 60%. Experiments 2 and 3 exam ined the effects of bilateral lesions on neuroanatomy and behavior. Bi lateral lesions were somewhat smaller than unilateral lesions, and as for unilateral lesions, degeneration in pre- and postcommissural forni x was seen only in SURG15 animals. The behavioral task used in Experim ents 2 and 3 was patterned single alternation, a memory-based appetiti ve learning discrimination. Earlier work has shown that damage to the infant hippocampus results in moderate deficits in this task at 30-s i ntervals and more substantial deficits at 60-s intertrial intervals. T his was not the case in the present studies: regardless of age at surg ery or time postlesion, all infant rats tested learned this discrimina tion at the two intertrial intervals. As has been recently reported fo r adult rats, excitotoxic lesions of the hippocampus in infant rats do not produce the same patterns of behavioral deficits as electrolytic lesions. (C) 1995 Academic Press, Inc.