A number of proteins implicated in immune reactions appear to be associated with the characteristic pathological features of Alzheimer's disease. Some are thought to alter the expression, production and processing of amyloid precursor protein (APP), whose amyloid metabolites may be associated with neurodegenerative changes.In this study, we examined the effect of the anti-inflammatory drugs, aspirin and dexamethasone, on the hippocampal expression of the APP isoforms 695, 714, 751, and 770. Halothane-anaesthetised rats received unilateral intrahippocampal (ih) injections of 50 nmol/mL ibotenic acid either 15 minutes or three weeks prior to an ipsilateral ih injection of 17 nmol/mL dexamethasone (n=3), 5.5 nmol/mL aspirin (n=3), or vehicle (n=3). Ibotenic acid has previously been shown to alter the hippocampal expression of APP mRNA isoforms (Hutchings et al. 1994). Additional subjects received dexamethasone or aspirin 1 hour before administration of the excitotoxin (n=3). Four hours later, rats were perfusion-fixed and brain sections taken for in-situ hybridization studies. These were incubated with 3 5 S-labelled oligonucleotide probes and subsequently exposed to photographic film.Ibotenic acid, in the presence of vehicle, reduced the expression of the 695 and 714 mRNA isoforms in the hippocampus and dentate gyrus whilst it increased the expression of the 751 and 770 mRNA isoforms. Both dexamethasone and aspirin failed to alter the ibotenic-acid induced changes in the hybridization signal of any APP isoform, this being independent of pre-treatment time. Similarly, pre-treatment with dexamethasone or aspirin did not protect against the effect of the excitotoxin.The results of this study indicate that aspirin and dexamethasone do not appear to protect against excitotoxin-induced changes in APP mRNA expression. It has been suggested that enhanced expression of some APP mRNA isoforms, possibly through inflammatory-type reactions, may contribute to the formation of Alzheimer-type lesions. Under the conditions used here, no effect was observed from use of the antiinflammatory agents but further investigation is needed.