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Modulation of p,p'-DDT-induced tremor by catecholaminergic agents
1Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514.
Toxicology and Applied Pharmacology
|November 1, 1987
Summary
p,p'-DDT exposure in rats caused tremors, modulated by specific neurotransmitter receptors. Alpha-1 and alpha-2 receptors influence DDT tremor, while dopamine and beta receptors may inhibit it.
Area of Science:
- Neurotoxicology
- Pharmacology
- Physiology
Background:
- p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) is an organochlorine pesticide known to cause neurotoxic effects, including tremors.
- The precise neurochemical mechanisms underlying DDT-induced tremor are not fully understood.
- Understanding these mechanisms is crucial for assessing neurotoxic risks and developing potential interventions.
Purpose of the Study:
- To investigate the role of specific neurotransmitter receptors in modulating p,p'-DDT-induced tremor in male Fischer 344N rats.
- To characterize the effects of alpha-adrenergic, beta-adrenergic, and dopaminergic receptor agonists and antagonists on DDT-induced motor activity.
Main Methods:
- Rats were administered p,p'-DDT (75 mg/kg) orally or corn oil (control).
- Tremor was quantified 8 hours later using spectral analysis of whole-body movements.
- Pharmacological challenges included subcutaneous injections of alpha-1 and alpha-2 antagonists (phenoxybenzamine, prazosin, yohimbine), beta antagonist (propranolol), alpha-2 agonist (clonidine), and dopamine agonists/antagonists (haloperidol, apomorphine).
Main Results:
- Phenoxybenzamine and prazosin (alpha-1 antagonists) decreased movement intensity in DDT-treated rats.
- Yohimbine (alpha-2 antagonist) and propranolol (beta antagonist) increased movement intensity and caused lethality in DDT-treated rats.
- Clonidine (alpha-2 agonist) decreased movement intensity in DDT-treated rats, while haloperidol (dopamine antagonist) increased it.
- Apomorphine (dopamine agonist) induced stereotypy in controls but did not significantly alter movement spectra in DDT-treated rats.
Conclusions:
- Alpha-1 adrenergic receptors appear to facilitate DDT-induced tremor.
- Alpha-2 adrenergic receptors seem to play an inhibitory role in modulating DDT tremor.
- Dopamine and beta receptors may be involved in the tonic inhibition of tremor caused by p,p'-DDT exposure.