Methylphenidate facilitates learning-induced amygdala plasticity
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Although methylphenidate (Ritalin) has been used therapeutically for nearly 60 years, the mechanisms by which it acutely modifies behavioral performance are poorly understood. Here we combined intra-lateral amygdala in vivo pharmacology and ex vivo electrophysiology to show that acute administration of methylphenidate, as well as a selective dopamine transporter inhibitor, facilitated learning-induced strengthening of cortico-amygdala synapses through a postsynaptic increase in AMPA receptor-mediated currents, relative to those in saline-treated rats. Furthermore, local administration of methylphenidate in the lateral amygdala enhanced cue-reward learning through dopamine D1 receptor-dependent mechanisms and suppressed task-irrelevant behavior through D2 receptor-dependent mechanisms. These findings reveal critical and distinct roles for dopamine receptor subtypes in mediating methylphenidate-induced enhancements of neural transmission and learning performance.
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Stimulants act on the amygdala, which is distributed with monoamine transporters, and strengthen the current of cortico-amygdala synapses, which enhance emotional memory retention and learning performance.
“stimulants act on the amygdala, which is distributed with monoamine transporters (i.e. DAT and NET inhabitation) and strengthen the current of cortico-amygdala synapses, which enhance emotional memory retention and learning performance”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Tye et al., 2010
The Results and Discussion (page not available) show that methylphenidate and a selective DAT inhibitor strengthen cortico-amygdala synapses and improve cue-reward learning performance in rats. They distinguish this acute effect from the improved memory retention observed with NET inhibition; the paper does not show that synaptic strengthening enhances emotional memory retention. The claim also generalizes findings about methylphenidate and specific inhibitors to stimulants broadly. (LLM, conf=0.86)
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- Authors
- Tye, K. M., Tye, L. D., Cone, J. J., Hekkelman, E. F., Janak, P. H., & Bonci, A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Janak, Patricia H
- Bonci, Antonello
- Venue
- Nature Neuroscience
- Published
- 2010-03-07
- Volume
- 13
- Issue
- 4
- Pages
- 475-481
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2988577
- OpenAlex
- W1979376494
- Cited by
- 89
- References
- 50
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 9 · 2023: 4 · 2022: 6 · 2021: 1 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 9
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA15096-01, R01DA015096)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- methylphenidate, lateral amygdala, synaptic plasticity, learning-induced plasticity, dopamine D1 receptor, dopamine D2 receptor, dopamine transporter inhibitors
- MeSH terms
- Amygdala, Animals, Learning, Male, Methylphenidate, Neuronal Plasticity, Rats, Sprague-Dawley, Rats
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