Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat
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Rationale Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug's dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized. Objectives The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults. Methods CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (n = 34) and adult (n = 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots. Results Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA. Conclusions Adolescents are protected from the aversive effe…
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MPH modulates neurotrophic factors involved in neuronal survival and plasticity, such as BDNF and its BDNF/NT-3 growth factor receptor (NTRK2); the effect of MPH over these factors is unclear, since some experiments report inhibition, whereas others report activation, improving BDNF plasma concentrations in children with ADHD.
“Furthermore, MPH has been reported to modulate neurotrophic factors involved in neuronal survival and plasticity, such as BDNF and its BDNF/NT-3 growth factor receptor (NTRK2); the effect of MPH over these factors is unclear, since some experiments report inhibition [145], whereas others report activation, improving BDNF plasma concentrations in children with ADHD [146].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [145]
More recent studies have shown that the expression of BDNF is downregulated by MPH.
“On the other hand, more recent studies have shown that the expression of BDNF is downregulated by MPH [145, 148].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [145]
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- Authors
- Wetzell, B. B., Muller, M. M., Cobuzzi, J. L., Hurwitz, Z. E., DeCicco-Skinner, K., & Riley, A. L.
- Affiliations
- American University (US)
- Corresponding author
- Wetzell, B. Bradley
- Riley, Anthony L.
- Venue
- Psychopharmacology
- Published
- 2014-02-22
- Volume
- 231
- Issue
- 8
- Pages
- 1493-1501
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W1979601992
- Cited by
- 17
- References
- 60
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 2
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- American University Research Archive
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- methylphenidate, conditioned taste avoidance, age differences, adolescents, insula, central amygdala, brain-derived neurotrophic factor, TrkB, drug reward, attention deficit hyperactivity disorder, neuroprotection
- MeSH terms
- Animals, Avoidance Learning, Cerebral Cortex, Conditioning, Classical, Dose-Response Relationship, Drug, Eating, Male, Methylphenidate, Phosphorylation, Saccharin, Blotting, Western, Signal Transduction, Rats, Sprague-Dawley, Dopamine Uptake Inhibitors, Brain-Derived Neurotrophic Factor, Receptor, trkB, Taste Perception, Central Amygdaloid Nucleus
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