Acute drug-induced spine changes in the nucleus accumbens are dependent on β-adducin

- Acute caffeine or quinpirole increases spine density & length in nucleus accumbens.
- A single injection of haloperidol has opposite effects.
- The effects of the 3 drugs are absent in mice lacking β-adducin.
- Phosphorylation of adducin is increased by quinpirole, haloperidol, and caffeine.
- DARPP-32 phosphorylation mediates the effects of the 3 drugs on adducin.

Chronic modifications of dopamine transmission alter striatal dendritic spines. Here, we show that spine density and length are increased in the nucleus accumbens 24 h after a single injection of caffeine or quinpirole, a dopamine D2/D3 dopamine receptors agonist, whereas the dopamine antagonist haloperidol has opposite effects. These effects are absent in mice lacking β-adducin, a protein that stabilizes actin/spectrin cortical cytoskeleton and modulates synaptic plasticity. Phosphorylation of adducin (Ser713 in β-adducin), which disrupts actin/spectrin interaction, is increased by quinpirole, haloperidol, or caffeine. We previously demonstrated that DARPP-32 interacts with β-adducin and facilitates its phosphorylation. Quinpirole increased DARPP-32 phosphorylation at Thr75 and haloperidol at Ser97, two modifications that can have similar consequences on adducin phosphorylation through distinct mechanisms. Experiments in DARPP-32 mutant mice confirmed that the apparently paradoxical similar effects of quinpirole and haloperidol on adducin phosphorylation may result from differential effects of these drugs on DARPP-32 phosphorylation at Thr75 and Ser97. Our data provide novel insights on how a single dose of widely used psychoactive drugs can affect spine plasticity in the nucleus accumbens, a component of the reward system.

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