Significance: Environmental enrichment (EE) is a neuroprotective strategy successfully employed in the treatment of cognitive deficits in different models of brain injury or disease, including Alzheimer’s disease. However, the models used to study the effects of EE include different aspects or components that go beyond the environmental changes, as animals submitted to EE also increase physical activity levels and social interaction. Here we show that EE neuroprotection in memory deficits related to amyloid-β neurotoxicity, rather than resulting from EE per se, may rely on increased physical activity and social interaction.

Significance: A brief exposure to a novel environment was recently shown to enhance the extinction of contextual fear probably through a protein synthesis-dependent process of synaptic tagging and capture in the hippocampus. Here we report that this finding can be generalized to the extinction of another fear-motivated task, one-trial inhibitory avoidance. This generalization is important because extinction is used in exposure therapy to treat posttraumatic stress disorder in humans, and this may derive from various forms of fear-related stress. In addition, here we show that the effect of novelty on fear extinction is dependent on dopamine D1 but not D5 receptors in the hippocampus. These findings could be applicable to the exposure therapy of fear memory disorders.