Acute, but not longer-term, exposure to environmental enrichment attenuates Pavlovian cue-evoked conditioned approach and Fos expression in the prefrontal cortex in mice

Abstract

Exposure to environmental enrichment can modify the impact of motivationally relevant stimuli. For instance, previous studies in rats have found that even a brief, acute (~1 day), but not chronic, exposure to environmentally enriched (EE) housing attenuates instrumental lever pressing for sucrose-associated cues in a conditioned reinforcement setup. Moreover, acute EE reduces corticoaccumbens activity, as measured by decreases in expression of the neuronal activity marker "Fos." Currently, it is not known whether acute EE also reduces sucrose seeking and corticoaccumbens activity elicited by non-contingent or "forced" exposure to sucrose cues, which more closely resembles cue exposure encountered in daily life. We therefore measured the effects of acute/intermittent (1 day or 6 day of EE prior to test day) versus chronic (EE throughout conditioning lasting until test day) EE on the ability of a Pavlovian sucrose cue to elicit sucrose seeking (conditioned approach) and Fos expression in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and nucleus accumbens (NAc) in mice. One day, but not 6 day or chronic EE , reduced sucrose seeking and Fos in the deep layers of the dorsal mPFC. By contrast, 1 day, 6 day, and chronic EE all reduced Fos in the shallow layers of the OFC. None of the EE manipulations modulated NAc Fos expression. We reveal how EE reduces behavioral reactivity to sucrose cues by reducing activity in select prefrontal cortical brain areas. Our work further demonstrates the robustness of EE in its ability to modulate various forms of reward-seeking across species.

Keywords: Fos; Pavlovian appetitive conditioning; cue reactivity; environmental enrichment; food seeking; prefrontal cortex.

FIGURE 1

(a) The environmentally enriched (EE) housing cage and the standard housing (SH) cage. Gray dashed arrows indicate the inside of the EE cage. 1 day, but not 6 day and 5 weeks, of EE attenuates sucrose seeking elicited by Pavlovian sucrose cues. (b) Experimental timeline for 5 weeks EE (administered before and during acquisition until test day), the 1 day and 6 day EE (administered post-acquisition), and Standard Housing (SH) controls. (c) Approach Score as a function of the Acquisition session. (d) Approach Score on test day (n = 31, 20, 22, 26 for SH, 5 weeks, 6 day, and 1 day groups, respectively). *p < 0.05 against mice in the SH condition. All data are expressed as mean ± SEM

FIGURE 2

EE differentially modulates Fos expression in the prefrontal cortex, but not nucleus accumbens (NAc), subareas following testing for sucrose seeking (n = 11–12 per group). (a) Fos expression in the prefrontal cortex and NAc. (b) Laminar-based analyses of Fos expression in prefrontal cortex subareas. Legend: OFC, orbitofrontal cortex; ACC, anterior cingulate cortex; PL, prelimbic cortex; IL, infralimbic cortex; NAc^Co and NAc^Sh, nucleus accumbens core and shell, respectively. *p < 0.05, **<0.01, compared with mice in SH condition. All data are expressed as mean ± SEM

FIGURE 3

Representations of coronal sections indicating regions used for Fos expression analyses in prefrontal cortex subareas adapted from Paxinos and Franklin (2001) (top panel). Representative images of Fos expression in prefrontal cortex subareas (bottom panel; white scale bar = 200 μm). Legend: II-III, shallow layers II-III; V-VI, deep layers V-VI