Cage-induced stereotypic behaviour in laboratory mice covaries with nucleus accumbens FosB/ΔFosB expression

Abstract

Stereotypic behaviour (SB) occurs in certain human disorders (e.g. autism), and animals treated with stimulants or raised in impoverished conditions, including laboratory mice in standard cages. Dysfunctional cortico-basal ganglia pathways have been implicated in these examples, but for cage-induced forms of SB, the relative roles of ventral versus dorsal striatum had not been fully ascertained. Here, we used immunohistochemical staining of FosB and ΔFosB to assess long-term activation within the nucleus accumbens and caudate-putamen of C57BL/6 mice. Housed in typical laboratory cages, these mice spontaneously developed different degrees of route-tracing, bar-mouthing and other forms of SB (spending 0% to over 50% of their active time budgets in this behaviour). The most highly stereotypic mice showed the most elevated FosB/ΔFosB activity in the nucleus accumbens. No such patterns occurred in the caudate-putamen. The cage-induced SB common in standard-housed mice thus involves elevated activity within the ventral striatum, suggesting an aetiology closer to compulsive gambling, eating and drug-seeking than to classic amphetamine stereotypies and other behaviours induced by motor loop over-activation.

The development of repetitive motor behaviors in deer mice: Effects of environmental enrichment, repeated testing, and differential mediation by indirect basal ganglia pathway activation

“…Unfortunately, no investigation of sex effects was available for comparison. Future investigations of other brain regions shown to be important in stereotypy (e.g., nucleus accumbens, frontal cortex; McBride and Hemmings, 2005; Phillips, Choleris, Ervin, Fureix, Harper, Reynolds, Niel, Mason, 2016; Güldenpfennig, Wet Wolmarans, du Preez, Stein, Harvey, 2011) might yield differences in female mice.…”

“…Unfortunately, no investigation of sex effects was available for comparison. Future investigations of other brain regions shown to be important in repetitive behavior (e.g., nucleus accumbens, frontal cortex; Güldenpfennig, Wet Wolmarans, du Preez, Stein, & Harvey, 2011;McBride & Hemmings, 2005;Phillips et al, 2016) might yield differences in female mice. Neuronal activation differences in basal ganglia nuclei of males and females have been reported previously.…”

VGLUT3 gates psychomotor effects induced by amphetamine

“…; Phillips et al . ). Furthermore, striatal over‐expression of ∆FosB predisposes to altered psychostimulants‐induced effects (Kelz et al .…”

“…Specific comparisons: (c) **p < 0.01 (WT D5 vs. WT D1 ),°°°p < 0.001 (VGLUT3cKO-5HT D5 vs. VGLUT3cKO-5HT D1 ); (f) **p < 0.01 (WT D5 vs. WT D1 ),°°p < 0.01 (VGLUT3cKO-5HT D5 vs. VGLUT3cKO-5HT D1 ). VGLUT3, vesicular glutamate transporter type 3. movements (stereotypies and/or dyskinesia) has been highlighted (Cao et al 2010;Engeln et al 2016;Phillips et al 2016). Furthermore, striatal over-expression of ΔFosB predisposes to altered psychostimulants-induced effects (Kelz et al 1999).…”

Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders

“…Behaviorally, ARBs can be divided into two groups -motor stereotypies and impulsive/compulsive behaviors [14][15][16]. The former include the repetition of purposeless movements and/or body postures, whereas the latter involve cognitive inflexibility and aberrant goal-oriented behaviors [17][18][19][20]. Clinical motor stereotypies include repetitive stereotypical motor movements (SMMs), critical for neuropsychiatric diagnostics.…”