Impact of Environmental Enrichment on Perineuronal Nets in the Prefrontal Cortex following Early and Late Abstinence from Sucrose Self-Administration in Rats.

Megan Slaker,Barbara A. Sorg,Jesse Barnes,Jeffrey W. Grimm,Judith Homberg

doi:10.1371/journal.pone.0168256

Megan Slaker, Barbara A. Sorg + Show 3 more

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https://doi.org/10.1371/journal.pone.0168256

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Abstract

Perineuronal nets (PNNs) are aggregates of extracellular matrix that form structures surrounding a subset of GABAergic interneurons. The staining intensity of PNNs appears to be related to plasticity. Environmental enrichment (EE) influences plasticity during adulthood: EE decreases the rewarding effects of drugs of abuse and diminishes both drug- and sucrose-seeking behavior. We determined the impact of EE on PNN intensity in the medial prefrontal cortex (mPFC) in rats trained to self-administer sucrose. We examined the number and intensity of PNNs within the prelimbic (PL), infralimbic (IL), and orbitofrontal (OF) regions of the mPFC of adult Long-Evans rats that were trained for sucrose self-administration followed by acute or chronic EE during abstinence and a cue-induced reinstatement test. Rats exposed to EE prior to a cue-induced reinstatement of sucrose seeking had an increase in PNN staining compared with rats in standard housing. Conversely, naïve rats given 1 day of EE had a decrease in PNN intensity in the PL, no change in the IL, and an increase in the OF. Our findings demonstrate that EE increases PNN intensity in the mPFC after sucrose training, suggesting that training enhances the ability of EE to increase PNN intensity. We further demonstrate an interaction between time of abstinence, duration of EE exposure, and cue-induced reinstatement. Our results suggest that increased PNN intensity after EE may alter the excitatory/inhibitory balance of mPFC neurons such that rats are less responsive to a sucrose cue.

Highlights

IntroductionExposure to an enriched environment increases learning and memory processes, dendritic branching, and synapse formation in several areas of the brain (for review see [1])
The environment has a profound impact on the brain and behavior
perineuronal net (PNN) from animals in the 30 d Abst + 1 d EE group did not display significantly higher staining intensity than PNNs from the control 1 d Abst group (Dunn’s multiple comparisons test, p = 0.17). These results suggest that exposure to EE during the entire length of abstinence prior to a cue-induced reinstatement of sucrose-seeking increases PNN intensity within the PL region

Summary

Introduction

Exposure to an enriched environment increases learning and memory processes, dendritic branching, and synapse formation in several areas of the brain (for review see [1]). Exposure to EE decreases cue-induced reinstatement of sucrose seeking [10,11,12] This decrease in behavior coincides with decreased protein expression of the immediately early gene, c-Fos, within areas of the brain important for reward-related behaviors, including the prefrontal cortex (PFC), amygdala, and nucleus accumbens [12,13,14]. While these studies demonstrate that EE decreases reward-seeking behaviors and point to several brain regions that may mediate this effect, the underlying mechanisms remain unknown

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