Role of homeostatic feedback mechanisms in modulating methylphenidate actions on phasic dopamine signaling in the striatum of awake behaving rats.

08:00 EDT 11th August 2019 | BioPortfolio

Summary of "Role of homeostatic feedback mechanisms in modulating methylphenidate actions on phasic dopamine signaling in the striatum of awake behaving rats."

Methylphenidate is an established treatment for attention-deficit hyperactivity disorder that also has abuse potential. Both properties may relate to blocking dopamine and norepinephrine reuptake. We measured the effects of methylphenidate on dopamine dynamics in freely moving rats. Methylphenidate alone had no effect on the amplitude of phasic responses to cues or reward. However, when administered with the D2 receptor antagonist raclopride, methylphenidate increased dopamine responses, while raclopride alone had no effect. Using brain slices of substantia nigra or striatum, we confirmed that methylphenidate effects on firing rate of nigral dopamine neurons and dopamine release from terminals are constrained by negative feedback. A computational model using physiologically relevant parameters revealed that actions of methylphenidate on norepinephrine and dopamine transporters, and the effects of changes in tonic dopamine levels on D2 receptors, are necessary and sufficient to account for the experimental findings. In addition, non-linear fitting of the model to the data from freely moving animals revealed that methylphenidate significantly slowed the initial cue response dynamics. These results show that homeostatic regulation of dopamine release in the face of changing tonic levels of extracellular dopamine should be taken into account to understand the therapeutic benefits and abuse potential of methylphenidate.


Journal Details

This article was published in the following journal.

Name: Progress in neurobiology
ISSN: 1873-5118
Pages: 101681


DeepDyve research library

PubMed Articles [17737 Associated PubMed Articles listed on BioPortfolio]

Use of cognitive enhancers: methylphenidate and analogs.

In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive substances (NPS). We aimed to re...

The roles of musical expertise and sensory feedback in beat keeping and joint action.

Auditory feedback of actions provides additional information about the timing of one's own actions and those of others. However, little is known about how musicians and nonmusicians integrate auditory...

Scaling laws of cell-fate responses to transient stress.

Analysis and modelling of dose-survival curves of cells and tissues are often used to assess therapeutic efficacy or environmental risks, much less to infer the intracellular regulatory mechanisms of ...

SH3BP4 Regulates Intestinal Stem Cells and Tumorigenesis by Modulating β-Catenin Nuclear Localization.

Wnt signals at the base of mammalian crypts play a pivotal role in intestinal stem cell (ISC) homeostasis, whereas aberrant Wnt activation causes colon cancer. Precise control of Wnt signal strength i...

The boundaries of the self: The sense of agency across different sensorimotor aspects.

The sense of agency (SoA) is the sensation of control over our actions. SoA is thought to rely mainly upon the comparison of predictions regarding the sensory outcomes of one's actions and the actual ...

Clinical Trials [5930 Associated Clinical Trials listed on BioPortfolio]

Methylphenidate to Improve Balance and Walking in MS

Methylphenidate is an amphetamine-like psychomotor stimulant drug currently approved for the treatment of attention-deficit hyperactivity disorder (ADHD), postural orthostasis tachycardia ...

The Role of Oxytocin in Modulating the Effects of Social Feedback on Achieving Personal Goals

To examine potential differential effects of receiving various social feedback on achieving personal goals,and whether oxytocin would modulate these effects.

PK/PD Pediatric ADHD Classroom Study

The purpose of this study is to evaluate the association between blood drug levels and the corresponding scores of commonly used behavioral instruments based upon data collected following ...

Methylphenidate in Treating Patients With Melanoma

RATIONALE: Methylphenidate may relieve some of the side effects of chemotherapy in patients with melanoma. It is not known whether receiving methylphenidate is more effective than receivin...

Regulation of Energy Balance and Metabolism - Mechanisms Behind and Beyond Obesity and Weight Loss

The study aims to investigate homeostatic and hedonic mechanisms regulating appetite, energy balance and metabolism in obesity and the effects of three distinct obesity treatments on these...

Medical and Biotech [MESH] Definitions

A mechanism of communication with a physiological system for homeostasis, adaptation, etc. Physiological feedback is mediated through extensive feedback mechanisms that use physiological cues as feedback loop signals to control other systems.

A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE.

A subfamily of MARVEL domain-containing proteins that are found in SYNAPTIC VESICLES, where they may play a role in modulating neuronal signaling.

A sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to DEXTROAMPHETAMINE.

A syndecan found at high levels in the developing LIMB BUDS. It may play a role in the regulation of MUSCULOSKELETAL DEVELOPMENT by modulating the effects of INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS.

Quick Search

DeepDyve research library

Searches Linking to this Article