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DDT-induced myoclonus: serotonin and alpha noradrenergic interaction
Research Communications in Chemical Pathology and Pharmacology
|February 1, 1979
Summary
p,p'' -DDT induces myoclonic activity in mice, which is reduced by L-5-hydroxytryptophan (L-5HTP) and alpha-receptor blockers. Serotonin depletion blocked these effects, suggesting a role for alpha-noradrenergic and serotonergic pathways in myoclonus.
Area of Science:
- Neuropharmacology
- Toxicology
- Neuroscience
Background:
- p,p'-DDT is an organochlorine insecticide known to induce neurological effects, including myoclonic activity in animal models.
- Serotonergic and noradrenergic systems are critical in regulating motor control and neuronal excitability.
- Understanding the neurochemical mechanisms underlying DDT-induced myoclonus can provide insights into broader neurological processes.
Purpose of the Study:
- To investigate the role of serotonergic and noradrenergic systems in p,p'-DDT-induced myoclonus in mice.
- To determine the effects of L-5-hydroxytryptophan (L-5HTP), serotonin uptake blockers, and alpha-receptor blockers on DDT-induced myoclonus.
- To elucidate the potential neural circuitry involved in this neurotoxic effect.
Main Methods:
- Administration of p,p'-DDT to mice to induce myoclonic activity.
- Treatment with various pharmacological agents including L-5HTP, serotonin uptake blockers, and alpha-receptor blockers.
- Depletion of endogenous brain serotonin using p-chlorophenylalanine to assess the involvement of serotonin.
- Evaluation of the antimyoclonic effects and potentiation of L-5HTP activity by different drug classes.
Main Results:
- p,p'-DDT (600 mg/kg) reliably induced myoclonic activity.
- L-5HTP (200 mg/kg), serotonin uptake blockers, phenoxybenzamine (5 mg/kg), and trazodone (5 mg/kg) reduced this activity.
- Depletion of brain serotonin with p-chlorophenylalanine (400 mg/kg) blocked the antimyoclonic action of these drugs, except for L-5HTP.
- Seven other alpha-receptor blockers potentiated the antimyoclonic activity of a lower dose of L-5HTP (50 mg/kg).
Conclusions:
- The findings suggest that both serotonergic and alpha-noradrenergic systems play a role in the neural circuit mediating p,p'-DDT-induced myoclonus.
- An inhibitory alpha-noradrenergic synapse may be involved in the pathway from serotonergic neurons to the motor response.
- This study provides evidence for a complex interplay between neurotransmitter systems in the neurotoxicity of DDT.