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Biomolecules
Special Issues
The Planarian Model in Pharmacology, Toxicology, and Neuroscience
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The Planarian Model in Pharmacology, Toxicology, and Neuroscience

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 2662

Special Issue Editor

Prof. Dr. Oné R. Pagán

E-Mail Website
Guest Editor
Department of Biology, West Chester University, West Chester, PA 19383, USA
Interests: pharmacology; physiology; neurobiology; biochemistry; regeneration

Special Issue Information

Dear Colleagues,

The main biological claim to fame of freshwater planarians and related flatworms is the fact that some species display an uncanny capacity for regeneration, including the complete (and correct) regeneration of their relatively complex nervous system. Planarians have been used to test a variety of chemical compounds since at least the 18th century. However, arguably the systematic study of the pharmacology of planarians began in the 1970s with the studies of Drs. G. Palladini, A. Carolei, G. Venturini, and their colleagues at the University of Rome, Italy, in the context of the dopaminergic and cholinergic systems and eventually, on the effects of the abused drug, cocaine, in this organism. Since then, the planarian pharmacology field has blossomed, alongside the use of planarians in scientific fields like toxicology and neurobiology, establishing planarians as mainstream animal models beyond regenerative and developmental biology. In this Special Issue, we are pleased to present a sample of cutting-edge research showcasing the application of the planarian model in pharmacology, toxicology, and neuroscience.

Prof. Dr. Oné R. Pagán
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • planarians
  • pharmacology
  • toxicology
  • neuroscience
  • neurotransmission
  • regeneration

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Published Papers (3 papers)

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Research

24 pages, 4230 KB  
Article
Retention and Distribution of Dopamine-Dependent Reward Memory in Regenerating Planaria
by Kenneth Samuel, Abigail K. Hakes, Easter S. Suviseshamuthu and Maria E. Fichera
Biomolecules 2026, 16(5), 649; https://doi.org/10.3390/biom16050649 (registering DOI) - 27 Apr 2026
Viewed by 360
Abstract
Memory is generally thought to be stored within centralized neural circuits. However, whether learned behaviors can persist in the absence of a brain remains unresolved. Planaria (Girardia spp.) possess a primitive cephalic ganglion and a remarkable capacity for regeneration, providing a unique [...] Read more.
Memory is generally thought to be stored within centralized neural circuits. However, whether learned behaviors can persist in the absence of a brain remains unresolved. Planaria (Girardia spp.) possess a primitive cephalic ganglion and a remarkable capacity for regeneration, providing a unique system to examine non-cephalic memory retention. The primary aim of this study was to determine whether sucrose-induced conditioned place preference (CPP) is retained in posterior, brainless planarian fragments. Planaria were trained using a Pavlovian conditioning paradigm in which an initially unpreferred surface was paired with a 10% sucrose solution, resulting in a robust shift in surface preference. Following amputation, anterior fragments containing the cephalic ganglion as well as posterior fragments lacking the brain preserved the conditioned preference, demonstrating that reward-associated memory is stored even outside the cephalic nervous system. As a secondary objective, we examined the role of dopaminergic reinforcement using a D1 dopamine receptor antagonist during training. While antagonist-treated planaria failed to develop a CPP, posterior fragments from these amputated planaria likewise showed no conditioned preference, indicating that dopamine-dependent signaling is essential for sucrose-associated memory formation across the body. These results provide support for the hypothesis that reward-associated memory in planaria is distributed beyond the brain and can be modulated by dopaminergic pathways, highlighting the utility of this model for exploring fundamental mechanisms of reward, memory, and potential pharmacological interventions. Full article
(This article belongs to the Special Issue The Planarian Model in Pharmacology, Toxicology, and Neuroscience)
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20 pages, 3910 KB  
Article
Red Midge Larvae Are an Invertebrate Alternative Diet to Beef Liver for Planarian Husbandry
by Jonah Pacis, Danielle Ireland, Evangeline Coffinas, Jerome Sheehan, Kate Sun and Eva-Maria S. Collins
Biomolecules 2025, 15(12), 1659; https://doi.org/10.3390/biom15121659 - 27 Nov 2025
Cited by 2 | Viewed by 1014
Abstract
Freshwater planarians are an emerging model for toxicology and neuroscience because of their amenability to rapid behavioral screening and remarkable ability to regenerate a cephalized nervous system. As invertebrates, planarians can help reduce the use of vertebrates in research; however, laboratories typically maintain [...] Read more.
Freshwater planarians are an emerging model for toxicology and neuroscience because of their amenability to rapid behavioral screening and remarkable ability to regenerate a cephalized nervous system. As invertebrates, planarians can help reduce the use of vertebrates in research; however, laboratories typically maintain planarians on diets of homogenized organic beef or chicken liver, raising ethical concerns with feeding a vertebrate diet. Organic liver is difficult to obtain, and preparation methods vary, introducing intra- and interlaboratory variability. Here, we show that Dugesia japonica planarians can be maintained for over a year on commercially available red midge larvae (RML), a natural prey of freshwater planarians. We found only minor effects on reproduction and gene expression. To explore dietary effects on behavior and chemical sensitivity, we compared the results of a chemical screen using dimethyl sulfoxide, diazinon, and fluoxetine on adult and regenerating D. japonica. We found that differences in potency and bioactivity for planarians on liver and RML diets were on par with inter-experiment variability of planarians fed the same diet. We also show that RNA interference is feasible with RML. Because RML requires no preparation and sustains planarian populations long-term, this invertebrate diet can substitute liver and help reduce the use of vertebrates in research. Full article
(This article belongs to the Special Issue The Planarian Model in Pharmacology, Toxicology, and Neuroscience)
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14 pages, 892 KB  
Article
Within- and Between-Subject Analyses of the Effects of Chronic Xylazine on Negative Phototaxis in Two Planarian Species
by Tom Byrne
Biomolecules 2025, 15(11), 1542; https://doi.org/10.3390/biom15111542 - 2 Nov 2025
Viewed by 802
Abstract
Xylazine, an adulterant found frequently in illicit fentanyl, has been implicated in causing several adverse effects in human recreational users, including skin lesions and complications in the treatment of opiate overdose. Despite these public health concerns, the literature on the basic behavioral effects [...] Read more.
Xylazine, an adulterant found frequently in illicit fentanyl, has been implicated in causing several adverse effects in human recreational users, including skin lesions and complications in the treatment of opiate overdose. Despite these public health concerns, the literature on the basic behavioral effects of xylazine is limited. Recent research has demonstrated that planarians show potential as an emerging and practical animal model for studying the behavioral effects of acute xylazine exposure. The goal of the current investigation was to evaluate the behavioral effects of chronic xylazine administration on negative phototaxis in two planarian species: Girardia tigrina and Schmidtea mediterranea. Three experiments were conducted. Overall, 10 µM of chronic xylazine exposure, arranged according to a multiple-baseline design, impaired negative phototaxis in S. mediterranea but not G. tigrina. An ABA reversal design indicated that behavioral effects in S. mediterranea abated when chronic xylazine was terminated. Finally, a between-group design replicated potential interspecies differences when G. tigrina and S. mediterranea were compared directly, with the latter showing significantly greater susceptibility to drug effects. This work provides evidence of the utility of a planarian model for studying the behavioral effects of xylazine and lays the foundation for further investigation into the chronic effects of the drug. Full article
(This article belongs to the Special Issue The Planarian Model in Pharmacology, Toxicology, and Neuroscience)
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