Dopamine and norepinephrine receptors participate in methylphenidate enhancement of in vivo hippocampal synaptic plasticity
Open accessAbstract
Attention-deficit hyperactive disorder (ADHD) is the most commonly studied and diagnosed psychiatric disorder in children. Methylphenidate (MPH, e.g., Ritalin) has been used to treat ADHD for over 50 years. It is the most commonly prescribed treatment for ADHD, and in the past decade it was the drug most commonly prescribed to teenagers. In addition, MPH has become one of the most widely abused drugs on college campuses. In this study, we examined the effects of MPH on hippocampal synaptic plasticity, which serves as a measurable quantification of memory mechanisms. Field potentials were recorded with permanently implanted electrodes in freely-moving mice to quantify MPH modulation of perforant path synaptic transmission onto granule cells of the dentate gyrus. Our hypothesis was that MPH affects hippocampal synaptic plasticity underlying learning because MPH boosts catecholamine signaling by blocking the dopamine and norepinephrine transporters (DAT and NET respectively). In vitro hippocampal slice experiments indicated MPH enhances perforant path plasticity, and this MPH enhancement arose from action via D1-type dopamine receptors and β-type adrenergic receptors. Similarly, MPH boosted in vivo initiation of long-term potentiation (LTP). While there was an effect via both dopamine and adrenergic receptors in vivo, LTP induction was more dependent on the MPH-induced action via D1-type dopamine receptors. Under biologically reasonable experimental conditions, MPH enhances hippocampal synaptic plasticity via catecholamine receptors.
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Drugs of abuse, such as nicotine and methylphenidate, recruit dopaminergic neurotransmission to influence synaptic plasticity within the hippocampus.
“Also, there is functional evidence that indicates that drugs of abuse, such as nicotine (Tang and Dani, 2009; Zhang et al., 2010) and methylphenidate (Jenson et al., 2015), recruit dopaminergic neurotransmission to influence synaptic plasticity within the hippocampus.”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Jenson et al., 2015
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“Also, there is functional evidence that indicates that drugs of abuse, such as nicotine (Tang and Dani, 2009; Zhang et al., 2010) and methylphenidate (Jenson et al., 2015), recruit dopaminergic neurotransmission to influence synaptic plasticity within the hippocampus.”
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- Authors
- Jenson, D., Yang, K., Acevedo-Rodriguez, A., Levine, A., Broussard, J. I., Tang, J., & Dani, J. A.
- Affiliations
- Baylor College of Medicine (US)
- University of Pennsylvania (US)
- Corresponding author
- Dani, John A.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 90
- Pages
- 23-32
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC4533926
- OpenAlex
- W2088570852
- Cited by
- 52
- References
- 86
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 7 · 2018: 7 · 2017: 4 · 2016: 9 · 2015: 3
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropharmacology (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NIDA DA09411, NINDS NS21229)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- methylphenidate, hippocampal synaptic plasticity, long-term potentiation, dopamine D1 receptor, beta-adrenergic receptors, catecholamine signaling, dopamine transporter, norepinephrine transporter, perforant path, dentate gyrus granule cells, attention deficit hyperactivity disorder, memory, field potentials
- MeSH terms
- Central Nervous System Stimulants, Animals, Dopamine, Dose-Response Relationship, Drug, Electric Stimulation, Electrodes, Implanted, Female, Male, Methylphenidate, Mice, Inbred C57BL, Neurons, Receptors, Adrenergic, Receptors, Dopamine, Theta Rhythm, Long-Term Potentiation, Patch-Clamp Techniques, Dentate Gyrus, Perforant Pathway, Tissue Culture Techniques
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