Long term exposure to combination paradigm of environmental enrichment, physical exercise and diet reverses the spatial memory deficits and restores hippocampal neurogenesis in ventral subicular lesioned rats

•VSL leads to spatial memory deficits and reduces adult hippocampal neurogenesis.•Combination paradigm reverses the spatial memory deficits and restores neurogenesis.•18 C.W. Diet helps the reversal of spatial memory deficits following VSL.•Subiculum is important for integrating spatial memory. Subiculum is an important structure of the hippocampal formation and plays an imperative role in spatial learning and memory functions. We have demonstrated earlier the cognitive impairment following bilateral ventral subicular lesion (VSL) in rats. We found that short term exposure to enriched environment (EE) did not help to reverse the spatial memory deficits in water maze task suggesting the need for an appropriate enriched paradigm towards the recovery of spatial memory. In the present study, the efficacy of long term exposure of VSL rats to combination paradigm of environmental enrichment (EE), physical exercise and 18 C.W. diet (Combination Therapy – CT) in reversing the spatial memory deficits in Morris water maze task has been studied. Ibotenate lesioning of ventral subiculum produced significant impairment of performance in the Morris water maze and reduced the hippocampal neurogenesis in rats. Post lesion exposure to C.T. restored the hippocampal neurogenesis and improved the spatial memory functions in VSL rats. Our study supports the hypothesis that the combination paradigm is critical towards the development of an enhanced behavioral and cognitive experience especially in conditions of CNS insults and the associated cognitive dysfunctions.