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Possible involvement of dopaminergic neurotransmitter system in dichlorvos induced delayed neurotoxicity
Sanjeev Choudhary1, Geetu Raheja, Vandana Gupta
1Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh -160 012, India.
Abstract:
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.
Insights
Dichlorvos exposure disrupts the dopamine system, causing delayed neurotoxicity. Nimodipine protects against these effects by preserving dopamine system function.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Organophosphate-induced delayed neurotoxicity (OPIDN) is a severe neurological condition.
- The role of the dopaminergic system in OPIDN pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the dopaminergic system's involvement in dichlorvos-induced delayed neurotoxicity.
- To evaluate nimodipine's protective effects against dichlorvos-induced neurotoxicity.
Main Methods:
- Rats were administered a single dose of dichlorvos (200 mg/kg).
- Dopamine, norepinephrine, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase, and monoamine oxidase (MAO) levels and activities were measured.
- Dopamine D2 receptor binding was analyzed using Scatchard plots.
- Nimodipine was co-administered with dichlorvos to assess its protective efficacy.
Main Results:
- Dichlorvos significantly increased dopamine and norepinephrine levels and TH and dopamine-beta-hydroxylase activities, while decreasing MAO activity.
- Dopamine D2 receptor analysis showed a significant decrease in both K(d) and B(max).
- Nimodipine administration prevented these neurochemical alterations and ameliorated behavioral deficits.
Conclusions:
- Alterations in the dopamine system are implicated in the mechanisms of dichlorvos-induced delayed neurotoxicity.
- Nimodipine demonstrates protective efficacy against OPIDN by maintaining dopaminergic neurotransmitter system homeostasis.