title: Actions of methylphenidate on dopaminergic neurons of the ventral midbrain.
abstract: BACKGROUND
  Methylphenidate has been suggested to exert its therapeutic effect mainly by blocking the dopamine transporter. In spite of the importance of this interaction, no detailed information is available yet on its actions on single dopaminergic neurons.
  
  
  METHODS
  We examined the effects of methylphenidate on dopaminergic neurons using electrophysiological recordings from rat midbrain slices.
  
  
  RESULTS
  Methylphenidate inhibited spontaneous firing and caused a membrane hyperpolarization in current clamp or an outward current in voltage clamp. These effects were antagonized by the D(2) receptor antagonist sulpiride. An acute dopamine-depleting treatment of the slices with the dopa-decarboxylase inhibitor carbidopa significantly reduced the effects of methylphenidate. This drug potentiated, in a concentration-dependent manner, cellular responses to exogenous dopamine application.
  
  
  CONCLUSIONS
  Our electrophysiological data are consistent with the hypothesis that methylphenidate inhibits dopamine transporter and suggest that the depression of firing is mediated by the release of newly synthesized dopamine which accumulates extracellularly due to inhibition of its reuptake.
authors.affiliation: Laboratory of Experimental Neurology, IRCCS-Fondazione Santa Lucia, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Federici
authors.forename: Raffaella
authors.initials: R
authors.lastname: Geracitano
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Mercuri
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002230:Carbidopa / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D008774:Methylphenidate; D013469:Sulpiride; D012110:Reserpine; D003042:Cocaine; D002230:Carbidopa; D004298:Dopamine