THE EFFECTS OF PERINATAL HYPOXIA ON THE BEHAVIORAL, NEUROCHEMICAL, AND NEUROHISTOLOGICAL TOXICITY OF THE METABOLIC INHIBITOR 3-NITROPROPIONIC ACID

3-nitropropionic acid (3-NPA) neurotoxicity and long-term effects of p erinatal hypoxia were evaluated in 18 adult rats. Hypoxia-insulted (I) and noninsulted (NI) rats were delivered by cesarean section. Hypoxic insult was effected by submerging dissected uterine horns in warmed s aline for 15 min. NI rats were delivered from the adjacent nonsubmerge d horns. At postnatal day 90, I and NI rats were trained to perform ta sks thought to measure behaviors dependent upon aspects of time estima tion (TE), motivation, and learning. At 12 months of age, rats were in jected i.p. with escalating doses of 3-NPA (5 mg/kg/day to a maximum o f 30 mg/kg/day) immediately after each test session and sacrificed at the end of treatment. Additional male rats were used as untreated cont rols. Although 3-NPA produced a dose-dependent impairment of performan ce in each task, the effects were qualitatively similar for each group . A significant difference between I and NI rats was, however, observe d in the TE task where NI rats completed less of the task at high dose s of 3-NPA compared to I rats. Compared to untreated controls, dopamin e concentrations were decreased in caudate nucleus of both I and NI ra ts after 3-NPA. Specific areas most frequently damaged included cerebr al cortex, hippocampal subfield CA1, thalamus, caudate nucleus, and th e cerebellum. Lesions usually were less extensive in the I rather than NI members of a littermate pair, suggesting a possible protective eff ect of perinatal hypoxia against subsequent 3-NPA neurotoxicity.