Research ArticlePharmacology

Antipsychotics Activate mTORC1-Dependent Translation to Enhance Neuronal Morphological Complexity

Sci. Signal.  14 Jan 2014:
Vol. 7, Issue 308, pp. ra4
DOI: 10.1126/scisignal.2004331

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Translating Antipsychotic Action

Many antipsychotic drugs are antagonists of the D2 dopamine receptor (D2R), including the typical antipsychotic haloperidol. Haloperidol stimulates the kinase Akt, which can activate the translation-stimulating pathway mediated by the kinase complex mTORC1. Bowling et al. used both cultured primary striatal neurons and in vivo studies in mice to show that haloperidol increases neuronal complexity through a pathway involving mTORC1 and the synthesis of a specific set of proteins, especially proteins associated with the cytoskeleton and components of the translational machinery. Thus, these results suggest a mechanism downstream of D2R by which antipsychotics produce both short-term and long-lasting changes in neuronal behavior.