Changes in environment are known to alter reward system responses, although the underlying mechanisms are unclear. Researchers show that DARPP-32 interacts directly with β-adducin in the mouse striatum to regulate structural and behavioral plasticity in response to novel environment and drug exposure.

Environmental enrichment has multiple effects on behavior, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known.

Researchers show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments’ fast-growing ends and regulate synaptic stability.

DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade.

Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response.

Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.

http://www.nature.com/ncomms/2015/151207/ncomms10099/full/ncomms10099.html