Long-term functional neurotoxicity of paraoxon and chlorpyrifos: behavioural and pharmacological evidence

• Published in: Neurotoxicology and teratology 2004-03, Vol.26 (2), p.305-317
• Main Authors: Sánchez-Santed, Fernando, Cañadas, Fernando, Flores, Pilar, López-Grancha, Matilde, Cardona, Diana
• Format: Article
• Language: English
• Subjects: Amphetamine - pharmacology; Amphetamine-induced place preference conditioning; Animals; Arecoline - pharmacology; Behavior, Animal - drug effects; Biological and medical sciences; Central Nervous System Stimulants - pharmacology; Chlorpyrifos; Chlorpyrifos - toxicity; Cholinergic Agonists - pharmacology; Cholinesterase Inhibitors - metabolism; Clozapine - pharmacology; Conditioning, Operant - drug effects; Dopamine Antagonists - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Fundamental and applied biological sciences. Psychology; Haloperidol - pharmacology; Insecticides - toxicity; Long-term neurotoxicity; Male; Maze Learning - drug effects; Medical sciences; Muscarinic Antagonists - pharmacology; Neurology; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - physiopathology; Paraoxon; Paraoxon - toxicity; Random Allocation; Rats; Rats, Wistar; Reaction Time - drug effects; Scopolamine Hydrobromide - pharmacology; Serotonin Antagonists - pharmacology; Spatial Behavior - drug effects; Spatial reversal learning; Time; Toxicology; Vertebrates: nervous system and sense organs
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/j.ntt.2003.10.008

Organophosphate (OP) compounds are chemicals widely used in agriculture, industry and households and even as chemical weapons. The major mechanism of acute toxic action is the inhibition of acetylcholinesterase (AChE), which is responsible for the degradation of the neurotransmitter acetylcholine. A chronic OP-induced neuropsychiatric disorder (COPIND), which could result from both long-term exposure to subclinical doses of OP and after acute intoxication, has been proposed. These reports claim to develop animal models that could parallel behavioural and cognitive effects and that could later help to elucidate the mechanisms involved in this long-term affectation of the central nervous system. The present study uses a series of behavioural tests to discern the short- and long-term effects of acute intoxications with paraoxon (Px) or chlorpyrifos (CPF). Our results suggest that months after acute exposure to these OPs functional central nervous system alterations can be detected using a repeated acquisition spatial task in the water maze, for CPF, and in amphetamine-induced place preference paradigm, for both Px and CPF.