The cognitive enhancing effects of methylphenidate are well established, but the mechanisms remain unclear. We recently demonstrated that methylphenidate boosts cognitive motivation by enhancing the weight on the benefits of a cognitive task in a manner that depended on striatal dopamine. Here, we considered the complementary hypothesis that methylphenidate might also act by changing the weight on the opportunity cost of a cognitive task, that is, the cost of foregoing alternative opportunity. To this end, 50 healthy participants (25 women) completed a novel cognitive effort-discounting task that required choices between task and leisure. They were tested on methylphenidate, placebo, as well as the selective D2-receptor agent sulpiride, the latter to strengthen inference about dopamine receptor selectivity of methylphenidate's effects. Furthermore, they also underwent an [F]DOPA PET scan to quantify striatal dopamine synthesis capacity. Methylphenidate boosted choices of cognitive effort over leisure across the group, and this effect was greatest in participants with more striatal dopamine synthesis capacity. The effects of sulpiride did not reach significance. This study strengthens the motivational account of methylphenidate's effects on cognition, and suggests that methylphenidate reduces the cost of mental labor by increasing striatal dopamine.
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http://dx.doi.org/10.1038/s41386-020-00834-1 | DOI Listing |
ACS Chem Neurosci
January 2025
Departments of Psychiatry and Neurology, Division of Molecular Therapeutics, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York 10032, United States.
Voluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons, which extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: low-frequency tonic activity that is intrinsically generated and superimposed high-frequency phasic bursts that are driven by synaptic inputs. acute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics than recordings.
View Article and Find Full Text PDFGeroscience
January 2025
Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Background: Rapid eye movement (REM) sleep behavior disorder (RBD) is an early and significant prodromal marker for Parkinson's disease (PD). While the association between RBD and PD has been well-documented, the underlying pathophysiology differentiating PD patients with RBD (PD-RBD +) from those without RBD (PD-RBD-) remained unclear. This study aims to investigate the possible relationship between RBD and striatal dopamine depletion in de novo PD patients.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
División de Neurociencias Básicas, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, SSa, Calzada México-Xochimilco 289, Arenal de Guadalupe, Ciudad de México 14389, Mexico.
Parkinson's disease is associated with the loss of more than 40% of dopaminergic neurons in the substantia nigra pars compacta. One of the therapeutic options for restoring striatal dopamine levels is the administration of L-3,4-dihydroxyphenylalanine (L-Dopa). However, Parkinson's disease patients on long-term L-Dopa therapy often experience motor complications, such as dyskinesias.
View Article and Find Full Text PDFNeuroscience
January 2025
Johns Hopkins University School of Medicine, Department of Neurology, and the Kennedy Krieger Institute, Baltimore, MD, United States.
Deer mice provide a valuable naturally occurring animal model for investigating pathophysiological mechanisms underlying repetitive behaviors. Prior investigations using this model have identified abnormalities in the cortico-basal ganglia circuitry, including alterations within the indirect pathway and levels of endogenous opioids in the frontal cortex. In this study, the behaviors of n = 7 mice were quantified, and their brains were sectioned.
View Article and Find Full Text PDFJ Nucl Med
January 2025
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Parkinson disease (PD) is a multisystem disorder marked by progressive dopaminergic neuronal degeneration in the substantia nigra, as well as nondopaminergic systems. Our aim was to investigate longitudinal changes in -(3-[F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (F-FP-CIT) binding at the putamen, substantia nigra, and raphe nuclei in PD. This retrospective cohort study enrolled 127 patients with PD, who underwent F-FP-CIT PET scans twice or more, and 71 age- and sex-matched healthy controls.
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