Related Experiment Video

Updated: Aug 10, 2026

Functional Evaluation of Biological Neurotoxins in Networked Cultures of Stem Cell-derived Central Nervous System Neurons
15:05

Functional Evaluation of Biological Neurotoxins in Networked Cultures of Stem Cell-derived Central Nervous System Neurons

Published on: February 5, 2015

On the development of behavioral tolerance to organophosphates. II: Neurophysiological aspects

B P Melchers1, H P van Helden

  • 1Medical Biological Laboratory TNO, Rijswijk, The Netherlands.

Pharmacology, Biochemistry, and Behavior
|February 1, 1990
PubMed

Insights

Chronic exposure to cholinesterase inhibitors like DFP and soman in rats revealed differing effects on behavioral tolerance. Neurophysiological analysis explored these distinctions, offering insights into inhibitor mechanisms.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Toxicology

Background:

  • Cholinesterase inhibitors (DFP, soman) induce varying behavioral tolerance in rats.
  • Biochemical analyses failed to explain these differential tolerance effects.
  • Nicotinic receptor availability remained unchanged despite low cholinesterase activity.

Purpose of the Study:

  • To investigate the neurophysiological basis for differential behavioral tolerance to DFP and soman.
  • To explore the effects of chronic cholinesterase inhibitor treatment on neuromuscular function.

Main Methods:

  • In vitro analysis of spontaneous quantal acetylcholine release from rat diaphragm muscles.
  • Measurement of miniature endplate potential (MEPP) frequency and amplitude.
  • Assessment of neuromuscular function sensitivity to additional inhibitor in vitro.

Main Results:

  • Chronic DFP treatment significantly decreased MEPP frequency.
  • Chronic soman treatment significantly increased MEPP amplitude.
  • Muscle strips from treated animals showed increased sensitivity to further inhibitor exposure.

Conclusions:

  • Neurophysiological differences may underlie the distinct behavioral tolerance observed between DFP and soman.
  • Increased sensitivity to inhibitors contrasts with the expected phenomenon of tolerance.
  • Further research is needed to fully elucidate the mechanisms of tolerance to cholinesterase inhibitors.

More Related Videos

Automated Multimodal Stimulation and Simultaneous Neuronal Recording from Multiple Small Organisms08:28

Automated Multimodal Stimulation and Simultaneous Neuronal Recording from Multiple Small Organisms

Published on: March 3, 2023

Behavioral Analysis of Locomotor Dysfunction in Drosophila melanogaster as a Readout for Neurotoxicity07:03

Behavioral Analysis of Locomotor Dysfunction in Drosophila melanogaster as a Readout for Neurotoxicity

Published on: July 18, 2025

Related Concept Videos

Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Indirect-Acting Cholinergic Agonists: Pharmacokinetics01:22

Indirect-Acting Cholinergic Agonists: Pharmacokinetics

Indirect-acting cholinergic agonists, or anticholinesterases, enhance the body's cholinergic activity by inhibiting acetylcholine's breakdown. They are categorized as reversible or irreversible agents based on their mechanism of action. They are further classified into short-acting, intermediate-acting, and long-acting agents based on their duration of action.
Reversible agents containing quaternary amines, such as neostigmine and edrophonium, are not easily absorbed orally because they are...
Anticholinesterase Agents: Poisoning and Treatment01:26

Anticholinesterase Agents: Poisoning and Treatment

Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.     
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is slower than the...