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 consequences of multiple ibotenic acid (IBO) injections into the hippocampus were examined in Sprague-Dawley rat pups. Rat pups were 11 or 15 days of age at the time of surgery (SURG11, SURG15), the dose of IBO was either 1 microgram in 1 microliter, 2.5 micrograms in 0.5 microliters, or 5 micrograms in 1 microliter for 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 used in Experiment 1 to examine the extent of neural damage following unilateral lesions and showed that the degeneration was primarily located in the hippocampus. The magnitude of the damage was greatest in younger pups and in those which received the higher of the two concentrations (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 subiculum. Mortality rates following multiple IBO injections were very high in infant rats, in some cases as high as 60%. Experiments 2 and 3 examined the effects of bilateral lesions on neuroanatomy and behavior. Bilateral lesions were somewhat smaller than unilateral lesions, and as for unilateral lesions, degeneration in pre- and postcommissural fornix was seen only in SURG15 animals. The behavioral task used in Experiments 2 and 3 was patterned single alteration, a memory-based appetitive learning discrimination. Earlier work has shown that damage to the infant hippocampus results in moderate deficits in this task at 30-s intervals and more substantial deficits at 60-s intertrial intervals. This was not the case in the present studies: regardless of age at surgery or time postlesion, all infant rats tested learned this discrimination at the two intertrial intervals. As has been recently reported for adult rats, excitotoxic lesions of the hippocampus in infant rats do not produce the same patterns of behavioral deficits as electrolytic lesions.
Lobaugh
N J
NJ
Department of Psychology, University of Texas at Austin 78712, USA.
Norton
D
D
Novak
K
K
Amsel
A
A
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007051:Ibotenic Acid / Q000494:pharmacology*; D011939:Mental Recall / Q000187:drug effects*; D009410:Nerve Degeneration / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology
D007051:Ibotenic Acid