An acetylcholinesterase-independent mechanism for neurobehavioral impairments after chronic low level exposure to dichlorvos in rats.
The present study was designed to explore an alternate mechanism of action other than acetylcholinesterase inhibition for the chronic, low-level exposure to dichlorvos, an organophosphate, in vivo. Dichlorvos, at dose of 1.0 as well as 6.0 mg/kg b. wt. for 12 weeks to rats showed impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests. Though higher dose of dichlorvos had a detrimental effect on acetylcholinesterase activity, no significant inhibition was seen with lower dose of dichlorvos for the same period of exposure i.e. 12 weeks. Muscarinic acetylcholine receptor binding studies revealed a decrease in the number of binding sites (B(max)) in low as well as high dose groups but the dissociation constant (K(d)) value was unaffected with both doses of dichlorvos. Use of selective ligands against M(1), M(2) and M(3) receptor subtypes indicated that M(2) is the major receptor subtype being affected by chronic low-level exposure to dichlorvos. Western blot analysis and immunofluorescence studies also confirmed these biochemical findings. Thus, the present study suggests that M(2) receptors may play a major role in the development of neurobehavioral impairments after chronic exposure to dichlorvos.
Verma
Suresh Kumar
SK
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Kumar
Vijay
V
Gill
Kiran Dip
KD
D000110:Acetylcholinesterase / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002908:Chronic Disease; D004006:Dichlorvos / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D008024:Ligands; D011976:Receptors, Muscarinic; D004006:Dichlorvos; D000110:Acetylcholinesterase