title: Dopamine and norepinephrine receptors participate in methylphenidate enhancement of in vivo hippocampal synaptic plasticity.
abstract: 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.
authors.affiliation: Department of Neuroscience, Center on Addiction, Learning, Memory, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jenson
authors.affiliation: Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Kechun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, Center on Addiction, Learning, Memory, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Acevedo-Rodriguez
authors.affiliation: Department of Neuroscience, Center on Addiction, Learning, Memory, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Levine
authors.affiliation: Department of Neuroscience, Center on Addiction, Learning, Memory, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: John I
authors.initials: JI
authors.lastname: Broussard
authors.affiliation: Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: johndani@upenn.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Dani
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D019580:Perforant Pathway / Q000187:drug effects / Q000502:physiology; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D013826:Theta Rhythm / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D000697:Central Nervous System Stimulants; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D008774:Methylphenidate; D004298:Dopamine
keywords: Dentate gyrus; LTP; Long-term potentiation; Memory; Perforant path; Reward