SEQUELAE OF PARENTERAL DOMOIC ACID ADMINISTRATION IN RATS - COMPARISON OF EFFECTS ON DIFFERENT METABOLIC MARKERS IN BRAIN

Parenterally administered domoic acid, a structural analog of the exci tatory amino acids glutamic acid and kainic acid, has specific effects on brain histology in rats, as measured usung different anatomic mark ers. Domoic acid-induced convulsions affects Limbic structures such as hippocampus and entorhinal cortex, and different anatomic markers can detect these neurotoxic effects to varying degrees, Here we report ef fects of domoic acid administration on quantitative indicators of brai n metabolism and gliosis. Domoic acid, 2.25 mg/kg i.p., caused stereot yped behavior and convulsions in approximately 60% of rats which recei ved it. Six to eight days after domoic acid or vehicle administration, the animals were processed to measure regional brain incorporation of the long-chain fatty acids [1-C-14]arachidonic acid ([C-14]AA) and [9 ,10-H-3]palmitic acid ([H-3]PA), or regional cerebral glucose utilizat ion (rCMR(glc)) using 2-[1-C-14]deoxy-D-glucose, by quantitative autor adiography. Others rats were processed to measure brain glial fibrilla ry acidic protein (GFAP) by enzyme-linked immunosorbent assay. Domoic acid increased GFAP in the anterior portion of cerebral cortex, the ca udate putamen and thalamus compared with vehicle. However, in rats tha t convulsed after domoic acid GFAP was significantly increased through out the cerebral cortex, as well as in the hippocampus, septum, caudat e putamen, and thalamus. Domoic acid, in the absence of convulsions, d ecreased relative [C-14]AA incorporation in the claustrum and pyramida l cell layer of the hippocampus compared with vehicle-injected control s, In the presence of convulsions, relative [C-14]AA incorporation was decreased in hippocampus regions CAl and CA2. Uptake of [H-3]PA into brain was unaffected. Relative rCMR(glc) decreased in entorhinal corte x following domoic acid administration with or without convulsions. Th ese results suggest that acute domoic acid exposure affects discrete b rain circuits by inducing convulsions, and that domoic acid-induced co nvulsions cause chronic effects on brain function that are reflected i n altered fatty acid metabolism and gliosis. (C) 1977 Elsevier Science B.V.