Effects of acute or chronic environmental enrichment on regional Fos protein expression following sucrose cue-reactivity testing in rats

Abstract

Exposure to environmental enrichment (EE) reduces sucrose seeking by rats with a history of sucrose self-administration. The present experiment examined whether acute or chronic EE also reduces brain Fos levels, a protein marker indicative of neuronal activation. Fos levels were also examined after either 1 or 30 days of forced abstinence to examine whether Fos levels vary with the incubation of sucrose craving. Fos expression was examined in 18 regions and was identified in brain slices using immunohistochemistry. Fos levels were higher in most regions after 30 d of forced abstinence and were decreased in most regions by either acute or chronic EE. Eleven regions had some statistically significant effect and/or interaction of EE or incubation on Fos; the most salient of these are listed here. In the prelimbic cortex there was an incubation of Fos and EE reduced Fos at both forced abstinence time points. In contrast, in the orbitofrontal cortex there was no Fos incubation but EE reduced Fos at both forced abstinence time points. An interaction of EE and incubation was observed in the anterior cingulate cortex and nucleus accumbens core and shell where Fos incubated but EE only decreased Fos at the Day 30 forced abstinence time point. In contrast, in the dorsolateral striatum Fos incubated, but EE robustly decreased Fos expression at both forced abstinence time points. These differential expression patterns provide rationale for more detailed, site-specific molecular functional studies in how they relate to the ability of EE to reduce sucrose seeking.

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

“…Following 30 d EE and cue-induced reinstatement, Fos levels in the PL and OF regions are decreased, whereas following 1 d EE and cue-induced reinstatement, Fos levels within the IL region are increased [12]. The Fos findings are the reverse of our findings within the PL and OF: when we observed an increase in PNN intensity, there is a decrease in Fos levels [12].…”

“…These rats represent a subset of animals used in a study examining brain regional c-Fos levels following acute or chronic EE and the incubation of sucrose craving. Detailed methodological information is found in the publication of that study, Grimm et al [12]. All procedures with these animals followed the guidelines outlined in the “PHS Policy on Humane Care and Use of Laboratory Animals (2002)” and were approved by the Western Washington University Institutional Animal Care and Use Committee.…”

“…Detailed information regarding the operant procedures is provided in Grimm et al [12]. A summary of the experimental timeline and groups is shown in Fig 1.…”

“…Exposure to EE either prior to or following drug-seeking behaviors (sensitization, conditioned place preference (CPP), and self-administration), decreases the rewarding effects of cocaine and methamphetamine and diminishes drug-seeking behavior [4–9]. Exposure to EE also decreases cue-induced reinstatement of sucrose seeking [10–12]. 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 [12–14].…”

“…Exposure to EE also decreases cue-induced reinstatement of sucrose seeking [10–12]. 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 [12–14]. 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.…”