Striatal adenosine A2A receptor involvement in normal and large nest building deer mice: Perspectives on compulsivity and anxiety

Large nesting expression in deer mice remains stable under conditions of visual deprivation despite heightened limbic involvement: Perspectives on compulsive‐like behavior

“…Specifically, we show that NNB, but not LNB, inflates over time (Figure 3a), irrespective of lighting condition. This finding is congruent with previous work in the model; however, whereas we previously argued this response of NNB mice to resemble an anxiety‐like manifestation after longer term social isolation (Saaiman et al., 2023), the present data regarding hippocampal noradrenergic involvement (see below), are counterintuitive to such a conclusion. Rather, it is likely that while NNB is founded on evolutionary conserved mechanisms that enable mice to nest (Lewarch & Hoekstra, 2018), prior experience may improve behavioral outcomes in this cohort.…”

“…While we hypothesized that LNB might be related to processes aimed at achieving "justright" outcomes, the present results refute such a conclusion. In fact, the performance of LNB mice in this work is in line with theories pointing a role of behavioral rigidity and habitual learning in compulsive symptom expression, both of which are linked with corticostriatal hyperactivation (Calabresi et al, 2014;Lanciego et al, 2012), as was also shown in LNB compared to NNB mice before (Saaiman et al, 2023).…”

“…Conversely, the expression of LNB is excessive, rigid, and representative of maximal habit‐like behavioral activation that is not subject to temporal or experiential influences. We have argued the same before (Wolmarans et al., 2022; Saaiman et al., 2023). Here, we base our conclusion also on the response of NNB and LNB to VD, where significant differences between the neatness indices of nests built by NNB and LNB mice were only observed under conditions of VD (Figure 4a,b).…”

“…Classification of LNB is primarily based on (i) the total nesting‐score generated over 7 days (i.e., the cumulative weight of all the cotton wool used to construct nests over 1 week), and (ii) the behavioral variance observed with respect to the between‐day nesting performance over this period, reflected as a percentage coefficient of variance (% CV) value (Wolmarans et al., 2016). For the purposes of this work, as well as all prior nesting studies done in our laboratory, LNB is broadly defined as nesting scores that group together within the upper quartile (75th percentile) of the total nesting score distribution and the lower quartile (25th percentile) of the % CV distribution (Saaiman et al., 2023) (Figure 2). In contrast, NNB is identified as total nesting scores that consistently clustered below the 50th percentile of the total score distribution.…”

“…While a detailed review of biobehavioral differences between NNB and LNB mice falls beyond the scope of the present work (see Wolmarans et al (2022), Saaiman et al (2023), Wolmarans et al (2018), and Scheepers et al (2019 for an overview), NNB and LNB expressing mice have also been studied for potential differences in their anxiety-like profiles. While the two cohorts do not separate in terms of their behavior in tests of generalized anxiety, that is, a standard open field test (Saaiman et al, 2023), certain traces of evidence point to differences in anxiety sensitivity that must be highlighted. Firstly, and as alluded to above, LNB, compared to NNB mice, are overly resistant to negative and aversive feedback and will voluntarily recruit nesting material despite being demotivated to do so through self-inflicted punishment, that is, electric foot shock (de Brouwer, Harvey, & Wolmarans, 2020).…”