Figure 5.

COX-2-specific inhibition fails to protect against LPS-induced working memory deficits, and does not affect disease-associated elevated hippocampal and thalamic PGE₂, but blocks LPS-induced increases in hypothalamic PGE₂. a, Working memory was assessed by alternation in the paddling T-maze. ME7 animals were challenged with LPS (100 μg/kg, i.p.; n = 9) or saline (n = 9) in the presence of the COX-2-specific inhibitor NS-398 administered at 8 mg/kg, i.p., 60 min before LPS injection. Control ME7 animals (ME7+LPS, n = 8) were challenged with LPS 60 min post-vehicle injection (33% DMSO). Data were analyzed by two-way ANOVA, and Bonferroni post hoc analyses followed significant main effects: *p < 0.05 with respect to saline challenged animals (ME7+NS-398). b, Hippocampal and thalamic PGE₂ levels were measured in NBH and ME7 animals in the presence or absence of NS-398 (8 mg/kg, i.p.). There was a significant main effect of disease by two-way ANOVA but no effect of COX-2 inhibition on PGE₂ concentrations (NBH+vehicle, n = 3; NBH+NS-398, n = 4; ME7+vehicle, n = 4; ME7+NS-398, n = 5). c, Hypothalamic PGE₂ was measured 2 h postchallenge with LPS or saline, in the presence (n = 5 per group) or absence (n = 4 per group) of NS-398 (4 mg/kg, i.p.). After a significant main effect by two-way ANOVA, Bonferroni post hoc tests revealed significant differences, as denoted by *p < 0.05 with respect to vehicle+saline, and ⁺p < 0.05 with respect to vehicle+LPS. All data have been presented as the mean ± SEM.