Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration
The medical psychostimulant methylphenidate (MP) is used to treat attention-deficit hyperactivity disorder and recreationally as a “cognitive enhancer”. MP is a dopamine reuptake inhibitor, but does not affect serotonin. Serotonin contributes to addiction-related gene regulation and behavior. Previo...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Addiction Neuroscience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772392523000743 |
| _version_ | 1797390341214568448 |
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| author | Lorissa Lamoureux Joel A. Beverley Michela Marinelli Heinz Steiner |
| author_facet | Lorissa Lamoureux Joel A. Beverley Michela Marinelli Heinz Steiner |
| author_sort | Lorissa Lamoureux |
| collection | DOAJ |
| description | The medical psychostimulant methylphenidate (MP) is used to treat attention-deficit hyperactivity disorder and recreationally as a “cognitive enhancer”. MP is a dopamine reuptake inhibitor, but does not affect serotonin. Serotonin contributes to addiction-related gene regulation and behavior. Previously, we showed that enhancing serotonin action by adding a selective serotonin reuptake inhibitor, fluoxetine (FLX), to MP potentiates MP-induced gene regulation in striatum and nucleus accumbens, mimicking cocaine effects. Here, we investigated the behavioral consequences of MP+FLX treatment. Young adult male rats received MP (5 mg/kg, i.p.) or MP+FLX (5 mg/kg each) daily for 6-8 days. Behavioral effects were assessed in an open-field test during the repeated treatment. Two weeks later the motor response to a cocaine challenge (25 mg/kg) and the rate of acquisition of cocaine self-administration behavior were determined. Our results demonstrate that FLX potentiates effects of MP on open-field behavior. However, we found differential behavioral responses to MP+FLX treatment, as approximately half of the rats developed high rates of focal stereotypies (termed “MP+FLX/high reactivity” group), whereas the other half did not, and only showed increased locomotion (“MP+FLX/low reactivity” group). Two weeks later, cocaine-induced locomotion and stereotypies were positively correlated with MP+FLX-induced behavior seen at the end of the repeated MP+FLX treatment. Moreover, the MP+FLX/high reactivity group, but not the low reactivity group, showed facilitated acquisition of cocaine self-administration. These results demonstrate that repeated MP+FLX treatment can facilitate subsequent cocaine taking behavior in a subpopulation of rats. These findings suggest that MP+FLX exposure in some individuals may increase the risk for psychostimulant use later in life. |
| first_indexed | 2024-03-08T23:09:22Z |
| format | Article |
| id | doaj.art-53719469280f49b8ba35ec98a29dfe41 |
| institution | Directory Open Access Journal |
| issn | 2772-3925 |
| language | English |
| last_indexed | 2024-03-08T23:09:22Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Addiction Neuroscience |
| spelling | doaj.art-53719469280f49b8ba35ec98a29dfe412023-12-15T07:27:19ZengElsevierAddiction Neuroscience2772-39252023-12-019100131Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administrationLorissa Lamoureux0Joel A. Beverley1Michela Marinelli2Heinz Steiner3Discipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA; Present address: Biologic Resources Laboratory, University of Illinois at Chicago, Chicago, IL 60612, USADiscipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USADiscipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA; Present address: Department of Neuroscience, The University of Texas at Austin, Austin, TX 78712, USADiscipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA; Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA; Corresponding author.The medical psychostimulant methylphenidate (MP) is used to treat attention-deficit hyperactivity disorder and recreationally as a “cognitive enhancer”. MP is a dopamine reuptake inhibitor, but does not affect serotonin. Serotonin contributes to addiction-related gene regulation and behavior. Previously, we showed that enhancing serotonin action by adding a selective serotonin reuptake inhibitor, fluoxetine (FLX), to MP potentiates MP-induced gene regulation in striatum and nucleus accumbens, mimicking cocaine effects. Here, we investigated the behavioral consequences of MP+FLX treatment. Young adult male rats received MP (5 mg/kg, i.p.) or MP+FLX (5 mg/kg each) daily for 6-8 days. Behavioral effects were assessed in an open-field test during the repeated treatment. Two weeks later the motor response to a cocaine challenge (25 mg/kg) and the rate of acquisition of cocaine self-administration behavior were determined. Our results demonstrate that FLX potentiates effects of MP on open-field behavior. However, we found differential behavioral responses to MP+FLX treatment, as approximately half of the rats developed high rates of focal stereotypies (termed “MP+FLX/high reactivity” group), whereas the other half did not, and only showed increased locomotion (“MP+FLX/low reactivity” group). Two weeks later, cocaine-induced locomotion and stereotypies were positively correlated with MP+FLX-induced behavior seen at the end of the repeated MP+FLX treatment. Moreover, the MP+FLX/high reactivity group, but not the low reactivity group, showed facilitated acquisition of cocaine self-administration. These results demonstrate that repeated MP+FLX treatment can facilitate subsequent cocaine taking behavior in a subpopulation of rats. These findings suggest that MP+FLX exposure in some individuals may increase the risk for psychostimulant use later in life.http://www.sciencedirect.com/science/article/pii/S2772392523000743PsychostimulantSerotonin reuptake inhibitorDopamineSerotoninStereotypiesAddiction |
| spellingShingle | Lorissa Lamoureux Joel A. Beverley Michela Marinelli Heinz Steiner Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration Addiction Neuroscience Psychostimulant Serotonin reuptake inhibitor Dopamine Serotonin Stereotypies Addiction |
| title | Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration |
| title_full | Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration |
| title_fullStr | Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration |
| title_full_unstemmed | Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration |
| title_short | Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration |
| title_sort | fluoxetine potentiates methylphenidate induced behavioral responses enhanced locomotion or stereotypies and facilitated acquisition of cocaine self administration |
| topic | Psychostimulant Serotonin reuptake inhibitor Dopamine Serotonin Stereotypies Addiction |
| url | http://www.sciencedirect.com/science/article/pii/S2772392523000743 |
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