Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: Potential role for 5-HT1B receptor
| Autor: | Sarah Ehrlich, Joel A. Beverley, Heinz Steiner, Vincent Van Waes |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Agonist medicine.medical_specialty medicine.drug_class Serotonin reuptake inhibitor Dynorphin Pharmacology Article Rats Sprague-Dawley Cellular and Molecular Neuroscience Fluoxetine Internal medicine Neural Pathways medicine Animals 5-HT receptor Regulation of gene expression business.industry Methylphenidate Drug Synergism Long-term potentiation Serotonin 5-HT1 Receptor Agonists Corpus Striatum Rats Endocrinology Gene Expression Regulation Receptor Serotonin 5-HT1B business medicine.drug |
| Zdroj: | Neuropharmacology. 89:77-86 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2014.08.024 |
| Popis: | Drug combinations that include the psychostimulant methylphenidate plus a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine are increasingly used in children and adolescents. For example, this combination is indicated in the treatment of attention-deficit/hyperactivity disorder and depression comorbidity and other mental disorders. Such co-exposure also occurs in patients on SSRIs who use methylphenidate as a cognitive enhancer. The neurobiological consequences of these drug combinations are poorly understood. Methylphenidate alone can produce gene regulation effects that mimic addiction-related gene regulation by cocaine, consistent with its moderate addiction liability. We have previously shown that combining SSRIs with methylphenidate potentiates methylphenidate-induced gene regulation in the striatum. The present study investigated which striatal output pathways are affected by the methylphenidate + fluoxetine combination, by assessing effects on pathway-specific neuropeptide markers, and which serotonin receptor subtypes may mediate these effects. Our results demonstrate that a 5-day repeated treatment with fluoxetine (5 mg/kg) potentiates methylphenidate (5 mg/kg)-induced expression of both dynorphin (direct pathway marker) and enkephalin (indirect pathway). These changes were accompanied by correlated increases in the expression of the 5-HT1B, but not 5-HT2C, serotonin receptor in the same striatal regions. A further study showed that the 5-HT1B receptor agonist CP94253 (3-10 mg/kg) mimics the fluoxetine potentiation of methylphenidate-induced gene regulation. These findings suggest a role for the 5-HT1B receptor in the fluoxetine effects on striatal gene regulation. Given that 5-HT1B receptors are known to facilitate addiction-related gene regulation and behavior, our results suggest that SSRIs may enhance the addiction liability of methylphenidate by increasing 5-HT1B receptor signaling. |
| Databáze: | OpenAIRE |
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