Abstract

To study how motivational factors modulate experience-dependent neurobehavioral plasticity, we modify a protocol of environmental enrichment (EE) in rats. We assumed that the benefits derived from EE might vary according to the level of incentive salience attributed to it. To enhance the rewarding properties of EE, access to the EE cage varied randomly from 2 to 48 h for 30 days (REE). The REE group was enriched only 50% of the time and was compared to standard housing and continuous EE (CEE) groups. As behavioral readout, we analyzed the spontaneous activity and the ultrasonic vocalizations (USVs) within the EE cage weekly, and in the open field test at the end of the experiment. In the cage, REE increased the utilization of materials, physical activity, and the rate of appetitive USVs. In the OF, the CEE-induced enhancements in novelty habituation and social signaling were equaled by the REE. At the neural level, we measured the expression of genes related to neural plasticity and epigenetic regulations in different brain regions. In the dorsal striatum and hippocampus, REE upregulated the expression of the brain-derived neurotrophic factor, its tropomyosin kinase B receptor, and the DNA methyltransferase 3A. Altogether, our results suggest that the higher activity within the cage and the augmented incentive motivation provoked by the REE boosted its neurobehavioral effects equaling or surpassing those observed in the CEE condition. As constant exposures to treatments or stimulating environments are virtually impossible for humans, restricted EE protocols would have greater translational value than traditional ones.

Highlights

  • Knowing about how animals react to different environmental conditions would contribute to explaining why environmental stimulation in humans benefits some subjects but not others, a crucial enigma about the complex relationship between experience and neurobehavioral plasticity

  • restricted and unpredictable EE (REE) Increases the Activity and the Rate of Appetitive ultrasonic vocalizations (USVs) in the Cage Several lines of evidence have shown that restricted or unpredictable access to rewarding stimuli increases both incentive motivation attributed to reward-predicting cues and approaching and consummatory responses toward the reward (Anselme et al, 2013; Brenes and Schwarting, 2014; Schultz, 2016; Kreisler et al, 2018)

  • Remodeling and modifying the materials and items of the EE cage was one of the behaviors in which the group differences were the greatest, with such activity being increasingly higher in REE rats

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Summary

Introduction

Knowing about how animals react to different environmental conditions would contribute to explaining why environmental stimulation in humans (e.g., physical and psychological therapies, exercise, and preventive or palliative treatments) benefits some subjects but not others, a crucial enigma about the complex relationship between experience and neurobehavioral plasticity. The study of how motivation contributes to the benefits of environmental stimulation has received little attention in health sciences, and even less in preclinical research. To study the likely role of motivation in the regulation of experience-dependent plasticity on brain and behavior, we first redesigned a protocol of environmental enrichment (EE) in rats and assessed its effects on different behavioral domains and the expression of genes related with neural plasticity (Figure 1; Table 1).

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