5-Fluorouracil impairs attention and dopamine release in rats

Jarmolowicz, David P.; Gehringer, Rachel C.; Lemley, Shea M.; Sofis, Michael J.; Kaplan, Sam V.; Johnson, Michael A.

doi:10.1016/j.bbr.2019.01.007

Cited by 23 publications

(14 citation statements)

References 28 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mice receiving a single injection of doxorubicin had slower glutamate uptake into cells in both the cortex and the dentate gyrus (Thomas et al , ). Similarly, a reduction in dopamine release in the striatum following injections of carboplatin (Kaplan et al , ) or 5‐fluorouracil (Jarmolowicz et al , ) was reported. Serotonin release was also reduced in the raphe nucleus after carboplatin injection (Kaplan et al , ).…”

Section: Introductionmentioning

confidence: 77%

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

2020

View full text Add to dashboard Cite

Chemotherapy is a life-saving treatment for cancer patients, but also causes long-term cognitive impairment, or "chemobrain", in survivors. However, several challenges, including imprecise diagnosis criteria, multiple confounding factors, and unclear and heterogeneous molecular mechanisms, impede effective investigation of preventions and treatments for chemobrain. With the rapid increase in the number of cancer survivors, chemobrain is an urgent but unmet clinical need. Here, we leverage the extensive knowledge in various fields of neuroscience to gain insights into the mechanisms for chemobrain. We start by outlining why the post-mitotic adult brain is particularly vulnerable to chemotherapy. Next, through drawing comparisons with normal aging, Alzheimer's disease, and traumatic brain injury, we identify universal cellular mechanisms that may underlie the cognitive deficits in chemobrain. We further identify existing neurological drugs targeting these cellular mechanisms that can be repurposed as treatments for chemobrain, some of which were already shown to be effective in animal models. Finally, we briefly describe future steps to further advance our understanding of chemobrain and facilitate the development of effective preventions and treatments.Cognitive complaints are common among cancer patients during and after chemotherapy. Cross-sectional and longitudinal studies suggest that short-term memory, working memory, and verbal ability are most frequently affected, followed by visuospatial memory, executive functions, and attention span (for meta-analyses, see

show abstract

Section: Introductionmentioning

confidence: 77%

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

2020

View full text Add to dashboard Cite

show abstract

“…The results showed that 5-FU impaired attentional shifting. Behavioral outcomes were also compared with the extent of dopamine release measured using fast-scan cyclic voltammetry, which showed decreased dopamine release persisted for a week after the second injection (Jarmolowicz et al 2019).…”

Section: -Fluorouracilmentioning

confidence: 99%

Animal models of chemotherapy-induced cognitive decline in preclinical drug development

et al. 2021

View full text Add to dashboard Cite

Rationale Chemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person’s day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment hypotheses and strategies. Objectives A methodical evaluation of scientific literature is required to understand cognitive changes associated with the use of chemotherapeutic agents in different preclinical studies. This review mainly emphasizes animal models developed with various chemotherapeutic agents individually and in combination, with their proposed mechanisms contributing to the cognitive dysfunction. This review also points toward the analysis of chemobrain in healthy animals to understand the mechanism of interventions in absence of tumor and in tumor-bearing animals to mimic human cancer conditions to screen potential drug candidates against chemobrain. Results Substantial memory deficit as a result of commonly used chemotherapeutic agents was evidenced in healthy and tumor-bearing animals. Spatial and episodic cognitive impairments, alterations in neurotrophins, oxidative and inflammatory markers, and changes in long-term potentiation were commonly observed changes in different animal models irrespective of the chemotherapeutic agent. Conclusion Dyscognition exists as one of the serious side effects of cancer chemotherapy. Due to differing mechanisms of chemotherapeutic agents with differing tendencies to alter behavioral and biochemical parameters, chemotherapy may present a significant risk in resulting memory impairments in healthy as well as tumor-bearing animals.

show abstract

“…Carboplatin was demonstrated to impair dopamine release and uptake in the zebrafish model of chemobrain-related studies ( Field et al, 2018 ). Similarly, a reduction in DA release in the striatum following injections of 5-FU was shown ( Jarmolowicz et al, 2019 ). Treatment with DOX impaired glutamate neurotransmission in the mouse frontal cortex and hippocampus.…”

Section: Central Neurotoxicity: Chemobrainmentioning

confidence: 84%

Mechanisms of Chemotherapy-Induced Neurotoxicity

et al. 2022

View full text Add to dashboard Cite

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients’ quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide analogs may cause direct and indirect neurotoxicity. In this review we discuss the main effects of chemotherapy on the peripheral and central nervous systems, including neuropathic pain, chemobrain, enteric neuropathy, as well as nausea and emesis. Understanding mechanisms involved in chemotherapy-induced neurotoxicity is crucial for the development of drugs that can protect the nervous system, reduce symptoms experienced by millions of patients, and improve the outcome of the treatment and patients’ quality of life.

show abstract

5-Fluorouracil impairs attention and dopamine release in rats

Cited by 23 publications

References 28 publications

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

Animal models of chemotherapy-induced cognitive decline in preclinical drug development

Mechanisms of Chemotherapy-Induced Neurotoxicity

Contact Info

Product

Resources

About