Methylphenidate Disrupts Social Play Behavior in Adolescent Rats
Open accessAbstract
Methylphenidate is the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), but its mechanism of action is incompletely understood. The cognitive effects of methylphenidate have been extensively studied, but little is known about its effects on spontaneous social behavior. During adolescence, rats display a characteristic, highly vigorous form of social behavior, termed social play behavior, which is of critical importance for social and cognitive development. We investigated the neurobehavioral mechanisms by which methylphenidate affects social play behavior in rats. Methylphenidate (0.3-3.0 mg/kg, s.c. or p.o.) abolished social play behavior, without altering general social interest. This effect of methylphenidate did not depend upon the baseline level of social play and was not secondary to changes in locomotion. Furthermore, the play-suppressant effect of methylphenidate was not subject to tolerance or sensitization. Methylphenidate blocked both the initiation to play and the responsivity to play initiation. The effect of methylphenidate was mimicked by the noradrenaline reuptake inhibitor atomoxetine, which is also used for the treatment of ADHD, and was blocked by an alpha-2 adrenoceptor antagonist. In addition, combined administration of subeffective doses of methylphenidate and atomoxetine suppressed social play. However, blockade of alpha-1 adrenoceptors, beta-adrenoceptors, or dopamine receptors did not alter the effect of methylphenidate. The…
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Drug doses were selected based on previous research.
“Drug doses were carefully selected based on previous research (Vanderschuren et al. 2008; Achterberg et al. 2014; Roche in house data), and doses were calculated as salt.”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Vanderschuren et al. 2008
The play-suppressant properties of methylphenidate are due to increased behavioural inhibition, whereby energetic behaviours that result in diminished attention for the environment are reduced.
“We have previously argued that the play-suppressant properties of methylphenidate are due to increased behavioural inhibition, whereby energetic behaviours that result in diminished attention for the environment are reduced (Vanderschuren et al. 2008).”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Vanderschuren et al. 2008
Treatment with methylphenidate in a social setting does not alter locomotion, yet suppresses social play.
“we have previously shown that treatment with methylphenidate in a social setting does not alter locomotion, yet suppresses social play (Vanderschuren et al. 2008).”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Vanderschuren et al. 2008
The specific reduction in social play after methylphenidate treatment is consistent with previous findings.
“This specific reduction in social play after methylphenidate treatment is consistent with previous findings (Beatty et al. 1982; Vanderschuren et al. 2008)”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Vanderschuren et al. 2008
Methylphenidate inhibits social play behaviour through indirect stimulation of alpha-2 adrenoceptors.
“we have demonstrated that methylphenidate inhibits social play behaviour through indirect stimulation of alpha-2 adrenoceptors (Vanderschuren et al. 2008; Achterberg et al. 2016a, b).”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Vanderschuren et al. 2008
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“The procedures for social play analysis were as previously described (Vanderschuren et al. 2008).”
InfluentialSelf-citation
- Authors
- Vanderschuren, L. J. M. J., Trezza, V., Griffioen-Roose, S., Schiepers, O. J. G., Van Leeuwen, N., De Vries, T. J., & Schoffelmeer, A. N. M.
- Affiliations
- University Medical Center Utrecht (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Vanderschuren, Louk J M J
- Venue
- Neuropsychopharmacology
- Published
- 2008-02-27
- Volume
- 33
- Issue
- 12
- Pages
- 2946-2956
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2580804
- OpenAlex
- W2087783707
- Cited by
- 105
- References
- 20
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 11 · 2018: 7 · 2017: 3 · 2016: 7 · 2015: 11 · 2014: 3 · 2013: 11 · 2012: 5
- FWCI
- 4.67
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-05-21)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- VU Research Portal (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Iris (Roma Tre University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute on Drug Abuse (R01DA022628)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- methylphenidate, social play, attention deficit hyperactivity disorder, norepinephrine uptake, atomoxetine, alpha2-adrenoceptors, behavioral inhibition, adolescent rats, adverse drug reactions, locomotion
- MeSH terms
- Atomoxetine Hydrochloride, Central Nervous System Stimulants, Animals, Attention Deficit Disorder with Hyperactivity, Behavior, Animal, Brain, Dose-Response Relationship, Drug, Exploratory Behavior, Male, Methylphenidate, Norepinephrine, Play and Playthings, Propylamines, Social Behavior, Rats, Wistar, Adrenergic Antagonists, Adrenergic Uptake Inhibitors, Rats
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