The Effects of Antipsychotics on the Synaptic Plasticity Gene <i>Homer1a</i> Depend on a Combination of Their Receptor Profile, Dose, Duration of Treatment, and Brain Regions Targeted

• Main Authors: Felice Iasevoli, Elisabetta Filomena Buonaguro, Camilla Avagliano, Annarita Barone, Anna Eramo, Licia Vellucci, Andrea de Bartolomeis
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: International Journal of Molecular Sciences
• Subjects: psychosis; synaptic plasticity; gene expression; dopamine; glutamate; haloperidol
• Online Access: https://www.mdpi.com/1422-0067/21/15/5555

Background: Antipsychotic agents modulate key molecules of the postsynaptic density (PSD), including the <i>Homer1a</i> gene, implicated in dendritic spine architecture. How the antipsychotic receptor profile, dose, and duration of administration may influence synaptic plasticity and the <i>Homer1a</i> pattern of expression is yet to be determined. Methods: In situ hybridization for <i>Homer1a</i> was performed on rat tissue sections from cortical and striatal regions of interest (ROI) after acute or chronic administration of three antipsychotics with divergent receptor profile: Haloperidol, asenapine, and olanzapine. Univariate and multivariate analyses of the effects of topography, treatment, dose, and duration of antipsychotic administration were performed. Results: All acute treatment regimens were found to induce a consistently higher expression of <i>Homer1a</i> compared to chronic ones. Haloperidol increased <i>Homer1a</i> expression compared to olanzapine in striatum at the acute time-point. A dose effect was also observed for acute administration of haloperidol. Conclusions: Biological effects of antipsychotics on <i>Homer1a</i> varied strongly depending on the combination of their receptor profile, dose, duration of administration, and throughout the different brain regions. These molecular data may have translational valence and may reflect behavioral sensitization/tolerance phenomena observed with prolonged antipsychotics.