Methylphenidate, but not citalopram, decreases impulsive choice in rats performing a temporal discounting task
Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often perform...
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| Published in | Frontiers in psychiatry Vol. 15; p. 1385502 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
Frontiers Media S.A
08.05.2024
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| Online Access | Get full text |
| ISSN | 1664-0640 1664-0640 |
| DOI | 10.3389/fpsyt.2024.1385502 |
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| Abstract | Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons.
Here, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay.
Methylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity.
Our results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity. |
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| AbstractList | Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons.
Here, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay.
Methylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity.
Our results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity. IntroductionDrugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity – though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons.MethodsHere, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay.ResultsMethylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity.DiscussionOur results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity. Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons.IntroductionDrugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons.Here, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay.MethodsHere, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay.Methylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity.ResultsMethylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity.Our results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity.DiscussionOur results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity. |
| Author | Ramanathan, Dhakshin S. Koloski, Miranda F. Terry, Alyssa Lee, Noelle |
| AuthorAffiliation | 2 Center of Excellence for Stress and Mental Health, VA San Diego Medical Center , San Diego, CA , United States 1 Mental Health, VA San Diego Medical Center , San Diego, CA , United States 3 Department of Psychiatry, University of California-San Diego , San Diego, CA , United States |
| AuthorAffiliation_xml | – name: 1 Mental Health, VA San Diego Medical Center , San Diego, CA , United States – name: 3 Department of Psychiatry, University of California-San Diego , San Diego, CA , United States – name: 2 Center of Excellence for Stress and Mental Health, VA San Diego Medical Center , San Diego, CA , United States |
| Author_xml | – sequence: 1 givenname: Miranda F. surname: Koloski fullname: Koloski, Miranda F. – sequence: 2 givenname: Alyssa surname: Terry fullname: Terry, Alyssa – sequence: 3 givenname: Noelle surname: Lee fullname: Lee, Noelle – sequence: 4 givenname: Dhakshin S. surname: Ramanathan fullname: Ramanathan, Dhakshin S. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38779546$$D View this record in MEDLINE/PubMed |
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| Keywords | impulsivity temporal discounting methylphenidate nucleus accumbens citalopram |
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| Title | Methylphenidate, but not citalopram, decreases impulsive choice in rats performing a temporal discounting task |
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