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

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.

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

“…Together with positive effects on function, we also observed a recovery in brain connectivity with improved global network feature and increased DS density and PNNs. These changes at the cellular level after EE have also been shown in a rat model of neonatal hypoxia-ischemia with preserved DSs [53] and in an addiction-based model with increased PNN density [56]. The improvement at both behavioral and structural level is crucial to demonstrate the actual effect of EE therapy, identifying those functions and regions more sensitive to its effects, and to support its implementation in clinical conditions.…”

Incubation of food craving in rats: A review

“…Nor were there sucrose craving incubation-related changes in neuroplasticityrelated brain derived neurotrophic factor protein levels (Grimm et al, 2003) in several brain regions examined. Finally, incubation of sucrose craving was not associated with changes in cortical (prelimbic, infralimbic, orbitofrontal) perineuronal net densities (Slaker, Barnes, Sorg, & Grimm, 2016). Serotonin 2C receptors have been associated with appetite (Halford & Harrold, 2012).…”

“…Serotonin 2C receptors have been associated with appetite (Halford & Harrold, 2012). Finally, incubation of sucrose craving was not associated with changes in cortical (prelimbic, infralimbic, orbitofrontal) perineuronal net densities (Slaker, Barnes, Sorg, & Grimm, 2016). These densities are hypothesized to be recruited to "stabilize" synapses and have been related to memory formation and retention (Slaker et al, 2018).…”

Cocaine memory reactivation induces functional adaptations of fast-spiking interneurons in the rat medial prefrontal cortex

“…PNNs are modified by a variety of stimuli, including cocaine exposure [34,59], cocaine-CPP acquisition [21], alcohol [60,61], nicotine self-administration [62], heroin self-administration [63], sleep deprivation [40],environmental enrichment [64], and consumption of high fat diets [32]. A majority of PV FSIs within the PL PFC are surrounded by PNNs, and previous work by our group has shown that the amount of cocaine exposure differentially affected PNN and PV expression [34].…”