Characterization of a differential reinforcement of low rates of responding task in non-deprived male and female rats: Role of Sigma-1 receptors
Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action i...
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| Published in | Neuropharmacology Vol. 200; p. 108786 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
01.12.2021
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| Subjects | |
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| Abstract | Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action is measured in ad libitum fed/watered subjects. Specifically, we first determined the effects of both sex and estrous cycle on impulsive action by systematically comparing male and estrous-synchronized female subjects. In addition, we evaluated the convergent validity of this modified DRL task by testing the effects of the D2R/5HT2AR antagonist, aripiprazole, and the noncompetitive NMDAR antagonist, MK-801. Finally, we tested the effects of the selective antagonist BD-1063 and agonist PRE-084 of Sigma-1 receptor (Sig-1R) on impulsive action using this modified DRL task. We found that female rats showed and increased inability to withhold a response when compared to males, and this effect was driven by the metestrus/diestrus phase of the estrous cycle. In addition, aripiprazole and MK-801 fully retained their capability to reduce and increase impulsive action, respectively. Finally, the selective Sig-1R antagonist, BD-1063 dose-dependently reduced the inability to withhold a response in both sexes, though more potently in female rats. In summary, we show that impulsive action, as measured in a modified DRL task which minimizes energy-homeostatic influences, is a function of both sex and estrous cycle. Furthermore, we validate the convergent validity of the task and provide evidence that Sig-1R antagonism may represent a novel pharmacological strategy to reduce impulsive action.
•A task to measure impulsive action in ad libitum fed/watered subjects was used.•In this task, female rats show higher impulsive action compared to males.•Females' impulsivity is driven by the diestrus phase of the estrous cycle.•Aripiprazole and MK-801 retain their ability to block and increase impulsivity.•The Sig-1R antagonist, BD-1063, reduces impulsive action in both sexes. |
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| AbstractList | Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action is measured in ad libitum fed/watered subjects. Specifically, we first determined the effects of both sex and estrous cycle on impulsive action by systematically comparing male and estrous-synchronized female subjects. In addition, we evaluated the convergent validity of this modified DRL task by testing the effects of the D2R/5HT2AR antagonist, aripiprazole, and the noncompetitive NMDAR antagonist, MK-801. Finally, we tested the effects of the selective antagonist BD-1063 and agonist PRE-084 of Sigma-1 receptor (Sig-1R) on impulsive action using this modified DRL task. We found that female rats showed and increased inability to withhold a response when compared to males, and this effect was driven by the metestrus/diestrus phase of the estrous cycle. In addition, aripiprazole and MK-801 fully retained their capability to reduce and increase impulsive action, respectively. Finally, the selective Sig-1R antagonist, BD-1063 dose-dependently reduced the inability to withhold a response in both sexes, though more potently in female rats. In summary, we show that impulsive action, as measured in a modified DRL task which minimizes energy-homeostatic influences, is a function of both sex and estrous cycle. Furthermore, we validate the convergent validity of the task and provide evidence that Sig-1R antagonism may represent a novel pharmacological strategy to reduce impulsive action.Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action is measured in ad libitum fed/watered subjects. Specifically, we first determined the effects of both sex and estrous cycle on impulsive action by systematically comparing male and estrous-synchronized female subjects. In addition, we evaluated the convergent validity of this modified DRL task by testing the effects of the D2R/5HT2AR antagonist, aripiprazole, and the noncompetitive NMDAR antagonist, MK-801. Finally, we tested the effects of the selective antagonist BD-1063 and agonist PRE-084 of Sigma-1 receptor (Sig-1R) on impulsive action using this modified DRL task. We found that female rats showed and increased inability to withhold a response when compared to males, and this effect was driven by the metestrus/diestrus phase of the estrous cycle. In addition, aripiprazole and MK-801 fully retained their capability to reduce and increase impulsive action, respectively. Finally, the selective Sig-1R antagonist, BD-1063 dose-dependently reduced the inability to withhold a response in both sexes, though more potently in female rats. In summary, we show that impulsive action, as measured in a modified DRL task which minimizes energy-homeostatic influences, is a function of both sex and estrous cycle. Furthermore, we validate the convergent validity of the task and provide evidence that Sig-1R antagonism may represent a novel pharmacological strategy to reduce impulsive action. Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action is measured in ad libitum fed/watered subjects. Specifically, we first determined the effects of both sex and estrous cycle on impulsive action by systematically comparing male and estrous-synchronized female subjects. In addition, we evaluated the convergent validity of this modified DRL task by testing the effects of the D R/5HT R antagonist, aripiprazole, and the noncompetitive NMDAR antagonist, MK-801. Finally, we tested the effects of the selective antagonist BD-1063 and agonist PRE-084 of Sigma-1 receptor (Sig-1R) on impulsive action using this modified DRL task. We found that female rats showed and increased inability to withhold a response when compared to males, and this effect was driven by the metestrus/diestrus phase of the estrous cycle. In addition, aripiprazole and MK-801 fully retained their capability to reduce and increase impulsive action, respectively. Finally, the selective Sig-1R antagonist, BD-1063 dose-dependently reduced the inability to withhold a response in both sexes, though more potently in female rats. In summary, we show that impulsive action, as measured in a modified DRL task which minimizes energy-homeostatic influences, is a function of both sex and estrous cycle. Furthermore, we validate the convergent validity of the task and provide evidence that Sig-1R antagonism may represent a novel pharmacological strategy to reduce impulsive action. Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action is measured in ad libitum fed/watered subjects. Specifically, we first determined the effects of both sex and estrous cycle on impulsive action by systematically comparing male and estrous-synchronized female subjects. In addition, we evaluated the convergent validity of this modified DRL task by testing the effects of the D 2 R/5HT 2A R antagonist, aripiprazole, and the noncompetitive NMDAR antagonist, MK-801. Finally, we tested the effects of the selective antagonist BD-1063 and agonist PRE-084 of Sigma-1 receptor (Sig-1R) on impulsive action using this modified DRL task. We found that female rats showed and increased inability to withhold a response when compared to males, ad this effect was driven by the metestrus/diestrus phase of the estrous cycle. In addition, aripiprazole and MK-801 fully retained their capability to reduce and increase impulsive action, respectively. Finally, the selective Sig-1R antagonist, BD-1063 dose-dependently reduced the inability to withhold a response in both sexes, though more potently in female rats. In summary, we show that impulsive action, as measured in a modified DRL task which minimizes energy-homeostatic influences, is a function of both sex and estrous cycle. Furthermore, we validate the convergent validity of the task and provide evidence that Sig-1R antagonism may represent a novel pharmacological strategy to reduce impulsive action. Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action is measured in ad libitum fed/watered subjects. Specifically, we first determined the effects of both sex and estrous cycle on impulsive action by systematically comparing male and estrous-synchronized female subjects. In addition, we evaluated the convergent validity of this modified DRL task by testing the effects of the D2R/5HT2AR antagonist, aripiprazole, and the noncompetitive NMDAR antagonist, MK-801. Finally, we tested the effects of the selective antagonist BD-1063 and agonist PRE-084 of Sigma-1 receptor (Sig-1R) on impulsive action using this modified DRL task. We found that female rats showed and increased inability to withhold a response when compared to males, and this effect was driven by the metestrus/diestrus phase of the estrous cycle. In addition, aripiprazole and MK-801 fully retained their capability to reduce and increase impulsive action, respectively. Finally, the selective Sig-1R antagonist, BD-1063 dose-dependently reduced the inability to withhold a response in both sexes, though more potently in female rats. In summary, we show that impulsive action, as measured in a modified DRL task which minimizes energy-homeostatic influences, is a function of both sex and estrous cycle. Furthermore, we validate the convergent validity of the task and provide evidence that Sig-1R antagonism may represent a novel pharmacological strategy to reduce impulsive action. •A task to measure impulsive action in ad libitum fed/watered subjects was used.•In this task, female rats show higher impulsive action compared to males.•Females' impulsivity is driven by the diestrus phase of the estrous cycle.•Aripiprazole and MK-801 retain their ability to block and increase impulsivity.•The Sig-1R antagonist, BD-1063, reduces impulsive action in both sexes. |
| ArticleNumber | 108786 |
| Author | Rice, Kenner C. Cottone, Pietro Iyer, Malliga R. Ferragud, Antonio Sabino, Valentina Blasio, Angelo Quadir, Sema G. |
| AuthorAffiliation | 3 Drug Design and Synthesis, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA 2 Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA 1 Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA |
| AuthorAffiliation_xml | – name: 2 Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA – name: 1 Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA – name: 3 Drug Design and Synthesis, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA |
| Author_xml | – sequence: 1 givenname: Valentina surname: Sabino fullname: Sabino, Valentina email: vsabino@bu.edu organization: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA – sequence: 2 givenname: Angelo surname: Blasio fullname: Blasio, Angelo organization: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA – sequence: 3 givenname: Antonio orcidid: 0000-0002-6739-007X surname: Ferragud fullname: Ferragud, Antonio organization: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA – sequence: 4 givenname: Sema G. surname: Quadir fullname: Quadir, Sema G. organization: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA – sequence: 5 givenname: Malliga R. surname: Iyer fullname: Iyer, Malliga R. organization: Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA – sequence: 6 givenname: Kenner C. orcidid: 0000-0002-1147-9147 surname: Rice fullname: Rice, Kenner C. organization: Drug Design and Synthesis, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA – sequence: 7 givenname: Pietro surname: Cottone fullname: Cottone, Pietro email: cottone@bu.edu organization: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34516984$$D View this record in MEDLINE/PubMed |
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| Keywords | MK-801 Impulsivity Impulsive action Estrous cycle Aripiprazole Sigma-1 receptor |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Valentina Sabino: Conceptualization, Validation, Formal analysis, Resources, Data Curation, Supervision, Writing - Original Draft, Supervision, Project administration, Funding acquisition. Angelo Blasio: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data Curation, Writing - Review & Editing. Ferragud Antonio: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data Curation, Writing - Review & Editing. Pietro Cottone: Conceptualization, Validation, Formal analysis, Resources, Data Curation, Writing - Original Draft, Supervision, Project administration, Funding acquisition. Kenner C Rice: Methodology, Validation, Resources, Data Curation, Writing - Review & Editing. Malliga R Iyer: Methodology, Validation, Resources, Data Curation, Writing - Review & Editing. Author contributions Sema G Quadir: Formal analysis, Investigation, Data Curation, Writing - Review & Editing. |
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| Snippet | Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we... |
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| SubjectTerms | Animals Aripiprazole Aripiprazole - pharmacology Behavior, Animal - drug effects Choice Behavior - drug effects Dizocilpine Maleate - pharmacology Dopamine D2 Receptor Antagonists - pharmacology Estrous cycle Estrous Cycle - drug effects Female Impulsive action Impulsive Behavior - drug effects Impulsivity Male MK-801 Piperazines - pharmacology Rats Rats, Wistar Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, sigma - drug effects Serotonin 5-HT2 Receptor Agonists - pharmacology Sigma-1 Receptor |
| Title | Characterization of a differential reinforcement of low rates of responding task in non-deprived male and female rats: Role of Sigma-1 receptors |
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