Omega-3-enriched fish oil (FO) and caloric restriction (CR) are nutritional therapeutic approaches that exert an important impact on brain function, behavior, memory, and neuroprotection. Here, we investigate the synergic effects of both therapeutic approaches combined (CR + FO) on behavior (memory, anxiety-like behavior, antidepressant-like behavior), as well as its association with hippocampal brain-derived neurotrophic factor (BDNF) concentrations. Adult male Wistar rats were divided into four dietary groups: Control group (C) - chow ad libitum; CR group - 30 % CR, considering C group food intake; FO group - FO-enriched chow ad libitum; and CR + FO group - FO-enriched 30 % CR chow. After 12 weeks of dietary treatment, behavioural analysis set was conducted, and hippocampal BDNF concentrations were measured.

FO group presented anxiolytic-like and antidepressant-like behaviors as well as improved memory in the Morris’ water maze. These effects were attenuated by the combined CR + FO treatment. FO group also presented higher BDNF concentrations.

There was a positive association between the number of entries in the platform quadrant in the MWM and hippocampal BDNF concentrations (β = 0.39; R² = 0.15; p = 0.042) and an inverse association between forced swim immobility time and BDNF concentrations (β = -0.39; R² = 0.15; p = 0.041). Taken together, our data showed that the 12-week FO dietary treatment promoted anxiolytic-like and antidepressant-like behaviors as well as memory improvement, and these effects were associated with BDNF concentrations. Synergic effects of interventions attenuated FO-related behavioral responses and BDNF concentrations and probably reduced hippocampal neuroplasticity.

富含 Omega-3 的鱼油 (FO) 和热量限制 (CR) 是对大脑功能、行为、记忆和神经保护产生重要影响的营养治疗方法。在这里，我们研究了两种治疗方法联合 (CR + FO) 对行为（记忆、焦虑样行为、抗抑郁样行为）的协同作用，以及其与海马脑源性神经营养因子 (BDNF) 浓度的关联。成年雄性 Wistar 大鼠分为四个饮食组：对照组 (C) -随意进食；CR 组 - 30 % CR，考虑到 C 组食物摄入量；FO 组 - FO-enriched Chow随意; 和 CR + FO 组 - 富含 FO 的 30% CR 饲料。饮食治疗12周后，进行行为分析组，并测量海马BDNF浓度。

FO 组在莫里斯水迷宫中表现出抗焦虑样和抗抑郁样行为以及改善的记忆。这些影响被 CR + FO 联合治疗减弱。FO 组也呈现更高的 BDNF 浓度。

MWM 平台象限中的条目数量与海马 BDNF 浓度（β = 0.39；R² = 0.15；p = 0.042）呈正相关，强迫游泳不动时间与 BDNF 浓度呈负相关（β = - 0.39；R² = 0.15；p = 0.041）。总之，我们的数据表明，12 周的 FO 饮食治疗促进了抗焦虑样和抗抑郁样行为以及记忆力的改善，并且这些影响与 BDNF 浓度有关。干预的协同效应减弱了 FO 相关的行为反应和 BDNF 浓度，并可能降低了海马神经可塑性。