Vilazodone, a Novel SSRI Antidepressant with 5-HT1A Partial Agonist Properties: Diminished Potentiation of Chronic Oral Methylphenidate-Induced Dynorphin Expression in the Striatum in Adolescent Male Rats.

Dynorphin Fluoxetine Gene Expression Methylphenidate Psychostimulant SSRI Striatum Vilazodone

Journal

Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963

Informations de publication

Date de publication:
28 Oct 2024
Historique:
received: 15 05 2024
accepted: 18 10 2024
medline: 28 10 2024
pubmed: 28 10 2024
entrez: 28 10 2024
Statut: aheadofprint

Résumé

Selective serotonin reuptake inhibitor (SSRI) antidepressants such as fluoxetine are used in combination with the medical psychostimulant methylphenidate (Ritalin) in a variety of treatments in children and adults. Unintended co-exposure to these psychotropic medications also occurs in patients on SSRIs who abuse methylphenidate as a "cognitive enhancer" or recreational drug. Preclinical research shows that SSRIs such as fluoxetine when given in conjunction with methylphenidate potentiate addiction-related gene regulation by methylphenidate in the striatum, consistent with the known facilitatory role for serotonin in psychostimulant-induced neuronal and behavioral changes. Moreover, fluoxetine combined with methylphenidate also facilitated subsequent acquisition of cocaine self-administration in adolescent rats, suggesting an increased addiction liability for methylphenidate. In the present study, we investigated the impact of a novel SSRI, vilazodone, on methylphenidate-induced gene regulation in adolescent male rats. In contrast to prototypical SSRIs such as fluoxetine, vilazodone also acts as a partial 5-HT1A serotonin receptor agonist and is thus proposed to temper serotonin input to the striatum. We compared the effects of chronic treatment (4 weeks) with vilazodone (10 mg/kg, twice daily) with those of fluoxetine (5 mg/kg, twice daily) on striatal dynorphin expression induced by oral methylphenidate treatment (30/60 mg/kg/day in drinking water, 8 h access daily). Our results demonstrate that, in contrast to fluoxetine, vilazodone had minimal or no potentiating effects on methylphenidate-induced dynorphin expression. This diminished impact on gene regulation was seen throughout the striatum, including the nucleus accumbens, where increased dynorphin expression has previously been associated with various aspects of addiction. Our findings suggest that vilazodone may serve as a better adjunct SSRI with reduced addiction-facilitating properties.

Identifiants

pubmed: 39466575
doi: 10.1007/s12035-024-04569-8
pii: 10.1007/s12035-024-04569-8
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Michael Hrabak (M)

Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

Rania Ahmed (R)

Behavioral Neuropharmacology and Neuroimaging Laboratory, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Michelle G Soriano (MG)

Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

Aidan Powell (A)

Behavioral Neuropharmacology and Neuroimaging Laboratory, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Panayotis K Thanos (PK)

Behavioral Neuropharmacology and Neuroimaging Laboratory, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Heinz Steiner (H)

Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 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, USA. heinz.steiner@rosalindfranklin.edu.

Classifications MeSH