5-HT 2A receptor activation by the 5-HT 2 receptor agonist DOI induced a transient increase in dendritic spine size, as well as phosphorylation of p21-activated kinase (PAK) in cultured cortical neurons. MUPP1 is enriched in postsynaptic density (PSD) fractions, is targeted to spines in pyramidal neurons, and enhances the localization of 5-HT 2A receptors to the cell periphery. It colocalizes with PSD-95 and with multiple PDZ protein-1 (MUPP1) in a subset of dendritic spines of rat cortical pyramidal neurons. Here we show that the 5-HT 2A receptor is present in a subset of spines, in addition to dendritic shafts. However, the role of 5-HT 2A receptors in regulating dendritic spine morphogenesis in cortical neurons is unknown.

The 5-HT 2A receptor is a target of several hallucinogens, antipsychotics, anxiolytics, and antidepressants, and it has been associated with several psychiatric disorders, conditions that are also associated with aberrations in dendritic spine morphogenesis. The 5-HT 2A serotonin receptor is the most abundant serotonin receptor subtype in the cortex and is predominantly expressed in pyramidal neurons.

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