Selective reduction of drebrin and actin in dendritic spines of hippocampal neurons by activation of 5-HT(2A) receptors

Abnormal architecture of dendritic spines is associated with neurodevelopmental and neurodegenerative diseases. The 5-HT(2A) receptor is a potential therapeutic target for mental illnesses and it is functionally and genetically associated with many types of psychiatric disorders. It has been reported that 5-HT(2A) receptor activation alters spine architecture. Although actin cytoskeleton has a key role in the regulation of spine architecture, it is not clarified whether 5-HT(2A)+ receptor activation affect the actin cytoskeleton in dendritic spines. In the present study, we examined the effect of 5-HT(2A) receptor activation on the actin cytoskeleton in dendritic spines of mature hippocampal neurons in low-density culture. Immunocytochemical analysis showed that 15 min exposure of 5-HT(2A) receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) significantly decreased the cluster densities of drebrin (control, 37.0±6.9 per 100 μm, DOI, 12.5±2.9) and F-actin (control, 18.3±4.9; DOI, 7.7±2.1) at dendritic spines without any detectable changes in the cluster densities of synapsin I and PSD-95. At the same time period DOI exposure did not affect spine architecture (spine density: control, 38.3±5.1 per 100 μm; DOI, 25.6±3.5; spine length: control, 1.99±0.18; DOI, 2.00±0.29; spine width: control, 0.72±0.06; DOI, 0.77±0.11). Thus, it is indicated that decrease of drebrin and F-actin can occur at the dendritic spines without morphological changes. Together our data suggest that 5-HT(2A) receptors activation is involved in the regulation of distribution of cytoskeleton in the dendritic spines.