The neuropharmacological basis for organochlorine-induced tremor and hyperexcitability was studied in rats. Both chlordecone and p,p'-DDT increased the release of brain norepinephrine and serotonin, while having marginal effects on dopamine; p,p'-DDT, but not chlordecone, was found to increase tissue levels of excitatory amino acids such as aspartate and glutamate in the brain stem and spinal cord. Pharmacological experiments to determine the functional significance of these neurochemical changes showed that cholinergic and serotonergic receptor antagonists attenuated the tremor produced by chlordecone, but enhanced that produced by p,p'-DDT. Blockade of alpha-noradrenergic receptors attenuated tremor produced by both organochlorines. Previous studies showed that pretreatment with the anticonvulsant phenytoin attenuated the tremor produced by p,p'-DDT, but enhanced that produced by chlordecone. Recent work extended this observation to augmentation of acoustic startle response produced by p,p'-DDT and chlordecone. Permethrin, a Type I pyrethrin believed to have the same mechanism of action as p,p'-DDT, produced the same neurochemical effects as p,p'-DDT; pretreatment with phenytoin also attenuated the neurological effects of permethrin. Intraventricular administration of calcium prior to the administration of p,p'-DDT or chlordecone attenuated or enhanced the tremorigenic effects produced by these agents, respectively. These experiments demonstrate the neurological manifestations produced by many of the organochlorines, such as tremor and augmented startle responsiveness, are similar, suggesting that they may activate a final common pathway; however, the neuropharmacological basis for the effect may be different.
