Dissociable rate-dependent effects of oral methylphenidate on impulsivity and D2/3 receptor availability in the striatum

Daniele Caprioli, Bianca Jupp, Young T. Hong, Stephen J. Sawiak, Valentina Ferrari, Laura Wharton, David J. Williamson, Carolyn McNabb, David Berry, Franklin I. Aigbirhio, Trevor W. Robbins, Tim D. Fryer, Jeffrey W. Dalley

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We have previouslyshown that impulsivityinratsislinkedtodecreaseddopamine D2/3 receptor availabilityintheventralstriatum.Inthe present study, we investigated, using longitudinal positron emission tomography (PET), the effects of orally administered methylpheni-date (MPH), a first-line treatment for attention deficit hyperactivity disorder, on D2/3 receptor availability in the dorsal and ventral striatum and related these changes to impulsivity. Rats were screened for impulsive behavior on a five-choice serial reaction time task. After a baseline PET scan with the D2/3 ligand [18F]fallypride, rats received 6 mg/kg MPH, orally, twice each day for 28 d. Rats were then reassessed for impulsivity and underwent a second [18F]fallypride PET scan. Before MPH treatment, we found that D2/3 receptor availability was significantly decreasedinthe left but not the right ventral striatumof high-impulse (HI) rats compared with low-impulse (LI) rats. MPH treatment increased impulsivity in LI rats, and modulated impulsivity and D2/3 receptor availability in the dorsal and ventral striatum of HI rats through inverse relationships with baseline levels of impulsivity and D2/3 receptor availability, respectively. However, we found no relationship between the effects of MPH on impulsivity and D2/3 receptor availability in any of the striatal subregions investigated. These findings indicate that trait-like impulsivity is associated with decreased D2/3 receptor availability in the left ventral striatum, and that stimulant drugs modulate impulsivity and striatal D2/3 receptor availability through independent mechanisms.

Original languageEnglish
Pages (from-to)3747-3755
Number of pages9
JournalJournal of Neuroscience
Issue number9
Publication statusPublished - 1 Jan 2015
Externally publishedYes


  • Addiction
  • Attention-deficit hyperactivity disorder
  • Dopamine
  • Methylphenidate
  • Nucleus accumbens
  • Positron emission tomography

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