Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice

Overt aggression, increased anxiety, and dysfunctional fear processing are often observed in individuals with conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH), a psychostimulant increasing dopamine and noradrenaline tone, is effective in reducing aggre...

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Publicado no:Frontiers in Psychiatry
Main Authors: Amanda Jager, Doranda Kanters, Femke Geers, Jan K. Buitelaar, Tamas Kozicz, Jeffrey C. Glennon
Formato: Artigo
Publicado em: Frontiers Media S.A. 2019-10-01
Assuntos:
Aggression
Animal
Anxiety
Attention-deficit hyperactivity disorder
Conduct disorder
Methylphenidate
Acesso em linha:https://www.frontiersin.org/article/10.3389/fpsyt.2019.00768/full
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spelling doaj-art-9c2fe955b01f4496a372d786efdf93c42025-08-19T20:07:20ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402019-10-011010.3389/fpsyt.2019.00768473638Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ MiceAmanda Jager0Doranda Kanters1Femke Geers2Jan K. Buitelaar3Tamas Kozicz4Tamas Kozicz5Jeffrey C. Glennon6Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboudumc, Nijmegen, NetherlandsDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboudumc, Nijmegen, NetherlandsDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboudumc, Nijmegen, NetherlandsDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboudumc, Nijmegen, NetherlandsDepartment of Anatomy, Donders Institute for Brain, Cognition and Behavior, Radboudumc, Nijmegen, NetherlandsDepartment of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, United StatesDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboudumc, Nijmegen, NetherlandsOvert aggression, increased anxiety, and dysfunctional fear processing are often observed in individuals with conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH), a psychostimulant increasing dopamine and noradrenaline tone, is effective in reducing aggression in both CD and ADHD individuals. However, it is unclear to which extent these effects of MPH are dose dependent. Here, the effects of acute intraperitoneal MPH (3 and 10 mg/kg) on aggression, anxiety, social behavior, and fear extinction were investigated in BALB/cJ mice. Previous studies in BALB/cJ mice have revealed high levels of aggression and anxiety that are associated with reduced top-down cortical control. Administration of 3 mg/kg MPH prolonged the attack latency and prevented escalation of aggression over time compared to vehicle-treated mice, while 10 mg/kg MPH increased number of bites and attacks. In addition, 3 mg/kg MPH decreased social interaction slightly. A strong anxiolytic effect was found after administration of both the 3 and 10 mg/kg doses in the elevated plus maze and the open-field test. In addition, while vehicle-treated BALB/cJ animals showed intact freezing, both doses of MPH decreased freezing to the unconditioned stimulus in a fear-conditioning paradigm. A long-lasting effect on fear extinction was visible after treatment with the 10 mg/kg dose. The data support a role for MPH in the regulation of anxiety, fear processing, and aggression in BALB/cJ mice, with the latter effect in a dose-dependent manner. The findings provide a further context for examining the effects of MPH in clinical disorders such as ADHD and CD.https://www.frontiersin.org/article/10.3389/fpsyt.2019.00768/fullaggressionanimalanxietyattention-deficit hyperactivity disorderconduct disordermethylphenidate
institution Directory of Open Access Journals
collection DOAJ
format Article
author Amanda Jager
Doranda Kanters
Femke Geers
Jan K. Buitelaar
Tamas Kozicz
Tamas Kozicz
Jeffrey C. Glennon
spellingShingle Amanda Jager
Doranda Kanters
Femke Geers
Jan K. Buitelaar
Tamas Kozicz
Tamas Kozicz
Jeffrey C. Glennon
Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice
Frontiers in Psychiatry
10.3389/fpsyt.2019.00768
Aggression
Animal
Anxiety
Attention-deficit hyperactivity disorder
Conduct disorder
Methylphenidate
author_facet Amanda Jager
Doranda Kanters
Femke Geers
Jan K. Buitelaar
Tamas Kozicz
Tamas Kozicz
Jeffrey C. Glennon
author_sort Amanda Jager
title Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice
title_short Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice
title_full Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice
title_fullStr Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice
title_full_unstemmed Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice
title_sort methylphenidate dose-dependently affects aggression and improves fear extinction and anxiety in balb/cj mice
publisher Frontiers Media S.A.
publisher_facet Frontiers Media S.A.
container_title Frontiers in Psychiatry
container_title_facet Frontiers in Psychiatry
issn 1664-0640
publishDate 2019-10-01
container_volume 10
doi 10.3389/fpsyt.2019.00768
description Overt aggression, increased anxiety, and dysfunctional fear processing are often observed in individuals with conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH), a psychostimulant increasing dopamine and noradrenaline tone, is effective in reducing aggression in both CD and ADHD individuals. However, it is unclear to which extent these effects of MPH are dose dependent. Here, the effects of acute intraperitoneal MPH (3 and 10 mg/kg) on aggression, anxiety, social behavior, and fear extinction were investigated in BALB/cJ mice. Previous studies in BALB/cJ mice have revealed high levels of aggression and anxiety that are associated with reduced top-down cortical control. Administration of 3 mg/kg MPH prolonged the attack latency and prevented escalation of aggression over time compared to vehicle-treated mice, while 10 mg/kg MPH increased number of bites and attacks. In addition, 3 mg/kg MPH decreased social interaction slightly. A strong anxiolytic effect was found after administration of both the 3 and 10 mg/kg doses in the elevated plus maze and the open-field test. In addition, while vehicle-treated BALB/cJ animals showed intact freezing, both doses of MPH decreased freezing to the unconditioned stimulus in a fear-conditioning paradigm. A long-lasting effect on fear extinction was visible after treatment with the 10 mg/kg dose. The data support a role for MPH in the regulation of anxiety, fear processing, and aggression in BALB/cJ mice, with the latter effect in a dose-dependent manner. The findings provide a further context for examining the effects of MPH in clinical disorders such as ADHD and CD.
topic Aggression
Animal
Anxiety
Attention-deficit hyperactivity disorder
Conduct disorder
Methylphenidate
topic_facet Aggression
Animal
Anxiety
Attention-deficit hyperactivity disorder
Conduct disorder
Methylphenidate
url https://www.frontiersin.org/article/10.3389/fpsyt.2019.00768/full
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