Proinflammatory cytokines play a central role in depression-like behaviour and apoptosis in the limbic system after myocardial infarction (MI). A PUFA n-3 diet or the combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 probiotics, when given before the ischaemic period, reduce circulating proinflammatory cytokines as well as apoptosis in the limbic system. The present study was designed to determine if the same nutritional interventions maintain their beneficial effects when started after the onset of the reperfusion period and attenuate depression-like behaviour observed after MI. MI was induced by the occlusion of the left anterior descending coronary artery for 40 min in rats. After the onset of reperfusion, animals were fed with a high-or low-PUFA n-3 diet, combined or not with one billion live bacteria of L. helveticus and B. longum. At 3 d post-MI, caspase-3 enzymatic activities and terminal 2 0 -deoxyuridine, 5 0 -triphosphate (dUTP) nick-end labelling (TUNEL)-positive cells were decreased in the CA1, dentate gyrus (DG) and amygdala with the high-PUFA n-3 diet, as compared to the three other diets. Probiotics attenuated caspase-3 activity and TUNEL-positive cells in the DG and the medial amygdala. At 2 weeks post-MI, depression-like behaviour was observed in the low-PUFA n-3 diet without probiotics-group, and this behaviour was attenuated with the high-PUFA n-3 diet or/and probiotics. These results indicate that a high-PUFA n-3 diet or the administration of probiotics, starting after the onset of reperfusion, are beneficial to attenuate apoptosis in the limbic system and post-MI depression in the rat.Key words: n-3 Fatty acids: Apoptosis: Limbic system: Diet: Behaviour: Hippocampus: Amygdala Depressive mood is common after myocardial infarction (MI) (1) and 20 % of MI patients develop an episode of major depression (2) . The association of depression with MI is critical, as the mortality rate is increased three to four times in depressed MI patients compared to non-depressed MI patients (3) . As the level of non-responders is still high with antidepressant treatments (4,5) and that the treatment may interfere with myocardial infarct size (6) , new antidepressant strategies need to be identified for such cases.The physiopathology of depression is complex and different mechanisms are involved (7) . Our previous work and that of others indicate that proinflammatory cytokines may play a key role in depression-like behaviour (8 -10) . Indeed, injection of proinflammatory cytokines is followed by depression-like behaviour (11) . Post-MI increased levels of proinflammatory cytokines are accompanied by apoptosis in the hippocampus and the amygdala, another physiopathological element of depression (8,9,12) .Dietary interventions can be used to prevent the post-MI elevation of proinflammatory cytokines. For example, we have shown that high-PUFA n-3 diets reduce the circulating level of TNFa after MI (13) . High-PUFA n-3 diets also reduce levels of monocyte chemotactic protein-1 (...