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p,p'-DDT-induced myoclonus in mice: the effect of enhanced 5-HT neurotransmission
Abstract:
The acute behavioural consequences of intragastric p,p'-DDT in high doses to mice are stimulus sensitive abrupt muscle jerks (myoclonus). The serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) ameliorated in contrast to the natural precursor tryptophan, the neurotoxin-induced myoclonus. The extracerebral decarboxylase inhibitor carbidopa and the selective 5-HT reuptake inhibitor paroxetine both enhanced the antimyoclonic action of 5-HTP. The effect was reversed by the 5-HT receptor blockers cinanserine and methysergide. The data add further evidence to a central serotonergic mechanism involved in p,p'-DDT induced myoclonus.
Insights
High doses of p,p-DDT cause muscle jerks in mice. The serotonin precursor 5-hydroxytryptophan (5-HTP) reduced these symptoms, suggesting a central serotonergic mechanism in p,p-DDT toxicity.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- p,p'-DDT is an organochlorine pesticide known to cause neurotoxicity.
- Acute exposure to high doses of p,p'-DDT in mice results in stimulus-sensitive myoclonus (muscle jerks).
- The precise neurochemical mechanisms underlying p,p'-DDT-induced myoclonus are not fully understood.
Purpose of the Study:
- To investigate the role of the central serotonergic system in p,p'-DDT-induced myoclonus.
- To evaluate the efficacy of serotonin precursors and modulators in ameliorating p,p'-DDT neurotoxicity.
Main Methods:
- Administration of p,p'-DDT to mice to induce myoclonus.
- Treatment with serotonin precursors (tryptophan, 5-hydroxytryptophan) and pharmacological agents (carbidopa, paroxetine, cinanserine, methysergide).
- Behavioral observation and assessment of myoclonus severity.
Main Results:
- Intragastric p,p'-DDT induced stimulus-sensitive myoclonus in mice.
- 5-hydroxytryptophan (5-HTP), but not tryptophan, significantly ameliorated the neurotoxin-induced myoclonus.
- Carbidopa and paroxetine enhanced the antimyoclonic effect of 5-HTP.
- The antimyoclonic action of 5-HTP was reversed by 5-HT receptor blockers (cinanserine, methysergide).
Conclusions:
- The findings provide evidence for a central serotonergic mechanism involved in p,p'-DDT-induced myoclonus.
- Modulation of the serotonin system, particularly through 5-HTP, offers a potential therapeutic strategy for p,p'-DDT neurotoxicity.
- Further research is warranted to elucidate the specific 5-HT receptor subtypes and pathways involved.