title: Involvement of dopaminergic and serotonergic systems in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats.
abstract: In view of extensive uses of lambda-cyhalothrin, a new generation type II synthetic pyrethroid, human exposure is quite imminent. The present study has therefore been carried out to investigate effect of lambda-cyhalothrin on brain dopaminergic and serotonergic systems and functional alterations associated with them. Post-lactational exposure to lambda-cyhalothrin (1.0 mg/kg or 3.0 mg/kg body weight, p.o.) from PD22 to PD49 caused a significant decrease in the motor activity and rota-rod performance in rats on PD50 as compared to controls. Decrease in motor activity in lambda-cyhalothrin treated rats was found to persist 15 days after withdrawal of exposure on PD65 while a trend of recovery in rota-rod performance was observed. A decrease in the binding of ³H-Spiperone, known to label dopamine-D2 receptors in corpus striatum associated with decreased expression of tyrosine hydroxylase (TH)-immunoreactivity and TH protein was observed in lambda-cyhalothrin treated rats on PD50 and PD65 compared to controls. Increase in the binding of ³H-Ketanserin, known to label serotonin-2A receptors in frontal cortex was observed in lambda-cyhalothrin exposed rats on PD50 and PD65 as compared to respective controls. The changes were more marked in rats exposed to lambda-cyhalothrin at a higher dose (3.0 mg/kg) and persisted even 15 days after withdrawal of exposure. The results exhibit vulnerability of developing rats to lambda-cyhalothrin and suggest that striatal dopaminergic system is a target of lambda-cyhalothrin. Involvement of serotonin-2A receptors in the neurotoxicity of lambda-cyhalothrin is also suggested. The results further indicate that neurobehavioral changes may be more intense in case exposure to lambda-cyhalothrin continues.
authors.affiliation: CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Post Box 80, MG Marg, Lucknow 226001, India.
authors.forename: Reyaz W
authors.initials: RW
authors.lastname: Ansari
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Shukla
authors.forename: Rajesh S
authors.initials: RS
authors.lastname: Yadav
authors.forename: Kavita
authors.initials: K
authors.lastname: Seth
authors.forename: Aditya B
authors.initials: AB
authors.lastname: Pant
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Singh
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Agrawal
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Islam
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Khanna
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects; D003337:Corpus Callosum / Q000737:chemistry / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D009570:Nitriles / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000032:analysis; D017448:Receptors, Dopamine D2 / Q000032:analysis; D059326:Serotonergic Neurons / Q000187:drug effects*
chemical_list: D009570:Nitriles; D011722:Pyrethrins; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; C037304:cyhalothrin