Vilazodone, a Selective Serotonin Reuptake Inhibitor with Diminished Impact on Methylphenidate-Induced Gene Regulation in the Striatum: Role of 5-HT1A Receptor.

Autor: Hrabak M; Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA., Moon C; Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA., Bolaños-Guzmán CA; Department of Psychological and Brain Sciences, Institute for Neuroscience, Texas A&M University, College Station, TX, 77843, USA., Steiner H; Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA. heinz.steiner@rosalindfranklin.edu.; Discipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA. heinz.steiner@rosalindfranklin.edu.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Apr; Vol. 61 (4), pp. 1907-1919. Date of Electronic Publication: 2023 Oct 09.
DOI: 10.1007/s12035-023-03688-y
Abstrakt: Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, are frequently combined with medical psychostimulants such as methylphenidate (Ritalin), for example, in the treatment of attention-deficit hyperactivity disorder/depression comorbidity. Co-exposure to these medications also occurs with misuse of methylphenidate as a recreational drug by patients on SSRIs. Methylphenidate, a dopamine reuptake blocker, produces moderate addiction-related gene regulation. Findings show that SSRIs such as fluoxetine given in conjunction with methylphenidate potentiate methylphenidate-induced gene regulation in the striatum in rats, consistent with a facilitatory action of serotonin on addiction-related processes. These SSRIs may thus increase methylphenidate's addiction liability. Here, we investigated the effects of a novel SSRI, vilazodone, on methylphenidate-induced gene regulation. Vilazodone differs from prototypical SSRIs in that, in addition to blocking serotonin reuptake, it acts as a partial agonist at the 5-HT1A serotonin receptor subtype. Studies showed that stimulation of the 5-HT1A receptor tempers serotonin input to the striatum. We compared the effects of acute treatment with vilazodone (10-20 mg/kg) with those of fluoxetine (5 mg/kg) on striatal gene regulation (zif268, substance P, enkephalin) induced by methylphenidate (5 mg/kg), by in situ hybridization histochemistry combined with autoradiography. We also assessed the impact of blocking 5-HT1A receptors by the selective antagonist WAY-100635 (0.5 mg/kg) on these responses. Behavioral effects of these drug treatments were examined in parallel in an open-field test. Our results show that, in contrast to fluoxetine, vilazodone did not potentiate gene regulation induced by methylphenidate in the striatum, while vilazodone enhanced methylphenidate-induced locomotor activity. However, blocking 5-HT1A receptors by WAY-100635 unmasked a potentiating effect of vilazodone on methylphenidate-induced gene regulation, thus confirming an inhibitory role for 5-HT1A receptors. Our findings suggest that vilazodone may serve as an adjunct SSRI with diminished addiction facilitating properties and identify the 5-HT1A receptor as a potential therapeutic target to treat addiction.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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