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

• Stereotypic behaviour (SB) occurs in certain human disorders (e.g. autism), and animals in impoverished conditions, including laboratory mice in standard cages.
• Dysfunctional cortico-basal ganglia pathways have been implicated, but for cage-induced SB, the precise regions had not been ascertained.
• We show that spontaneously highly stereotypic mice show the most elevated FosB/ΔFosB activity in the nucleus accumbens.
• No such patterns occurred in the caudate-putamen.
• This suggests that the SB common in standard-housed mice has an aetiology akin to compulsive gambling and drug-seeking.

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.