Poster Presentation The International Congress of Neuroendocrinology 2014

The cyclooxygenase-eicosanoid pathway and stress-induced spatial learning deficits (#127)

Denovan P Begg 1
  1. University of New South Wales, UNSW Sydney, NSW, Australia

Dietary polyunsaturated fatty acids (PUFA) are precursors to eicosanoids, there is some evidence to suggest that dietary ω-3 PUFA have beneficial effects relating to stress, mood disorders and memory performance1. We have recently demonstrated that the visuospatial cognitive deficits that occur with dietary ω-3 PUFA deficiency are mediated by the cyclooxygenase (COX)-eicosanoid pathway2. Here, we examined the effect of dietary ω-3 PUFA and COX inhibition on a novel model of stress induced memory impairment in the rat. In experiment 1, rats were placed on one of two semi-synthetic experimental diets six weeks prior to behavioural testing. Diets were either deficient in (DEF) or supplemented with (SUP) ω-3 PUFA. Groups underwent 15-minute forced-swim-stress (FS1) or no swim-stress (NS1). The following day animals were either tested in a Y-maze (Y2), to assess visuospatial memory performance, or for a second time (5-minutes) in the forced-swim apparatus (FS2), to assess learned helplessness. Therefore, in total there were six groups SUP-FS1/FS2, DEF-FS1/FS2, SUP-FS1/Y2, DEF-FS1/Y2, SUP-NS1/Y2 and DEF-NS1/Y2 (n=12/grp). Swim stress reduced spatial memory performance in the Y-maze (DEF-FS1/Y2), when compared with the unstressed group (DEF-NS1/Y2) for animals on a DEF diet. The SUP diet prevented the memory impairments associated with stress, SUP animals (SUP-FS1/FS2) also spent less time immobile in the forced swim test than the DEF group (DEF-FS1/FS2). In a second experiment animals on a DEF diet were treated with the COX-inhibitor (DEF-CI) or vehicle (DEF-V), DEF-CI animals led to improved spatial memory performance relative to DEF-V, in addition, CRF in the PVN of the DEF-CI group was reduced relative to the DEF-V group. In conclusion, similar to previous reports, our results demonstrate that ω-3 PUFA reduce learned helplessness in the rat3. The results presented establish that dietary ω-3 PUFA prevent stress induced memory impairment via inhibition of the cyclooxygenase (COX)-eicosanoid pathway.

  1. Ferraz AC, Delattre AM, Almendra RG, Sonagli M, Borges C, Araujo P, Andersen ML, Tufik S, Lima MM. Chronic ω-3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol. Behav Brain Res. 2011; 219(1):116-22.
  2. Hafandi A, Begg DP, Premaratna SD, Sinclair AJ, Jois M, Weisinger RS. Dietary repletion with ω3 fatty acid or with COX inhibition reverses cognitive effects in F3 ω3 fatty-acid-deficient mice. Comp Med. 2014; 64(2):106-9.
  3. Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005;57(4):343-50.