Possible involvement of dopaminergic neurotransmitter system in dichlorvos induced delayed neurotoxicity.
The present investigation was carried out to elucidate the possible involvement of the dopaminergic neurotransmitter system in the development of dichlorvos induced delayed neurotoxicity in the rat and to assess the protective efficacy of nimodipine against OPIDN (Organophosphate induced delayed neurotoxicity). Single subcutaneous dose of dichlorvos (200 mg/kg body weight) resulted in marked changes in the dopaminergic neurotransmitter system in terms of increased levels of both dopamine and norepinephrine along with significant increase in the activity of both the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase. This increase was accompanied with a concomitant decrease in the activity of the major degradative enzyme, monoamine oxidase. Scatchard plot analysis revealed a significant decrease in both K(d) and B(max) for dopamine D2 receptors. Administration of nimodipine, a centrally acting calcium channel blocker, along with dichlorvos restricted all these alterations to within control values and could also ameliorate certain behavioural deficits by maintaining the dopaminergic neurotransmitter system. The study underlines the importance of alterations in the dopamine system as a possible causative mechanism behind the behavioural and functional changes associated with delayed neurotoxicity.
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh -160 012, India.
Sanjeev
S
Choudhary
Geetu
G
Raheja
Vandana
V
Gupta
Kiran Dip
KD
Gill
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D004006:Dichlorvos / Q000008:administration & dosage / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D007279:Injections, Subcutaneous; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008995:Monoamine Oxidase / Q000032:analysis; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D002121:Calcium Channel Blockers; D007306:Insecticides; D017448:Receptors, Dopamine D2; D009553:Nimodipine; D004006:Dichlorvos; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D008995:Monoamine Oxidase; D004298:Dopamine; D009638:Norepinephrine