The purpose of this research is to study the role of the brain stem and spinal cord in motor dysfunction, such as tremor and hyperreflexia, which are signs frequently associated with neurological disorders, such as Parkinson's and Alzheimer's Disease. These investigations used p,p1-DDT, which interferes with Na+ channels causing repetitive firing of motor neurons. A potential facilitative role of spinal alpha1 receptors was hypothesized and examined by intrathecally infusing prazosin, an alpha1 receptor blocker, and in vivo binding techniques. The time and dose-dependent tremor produced by p,p1-DDT has been shown previously to be blocked by phenytonin, which acts on Na+ channels, and mephenesin, which blocks polysynaptic transmission in the spinal cord. Intrathecal administration of prazosin tended to reduce tremor produced by p,p1-DDT, but did so at doses that also reduced ambient levels of motor movement. Larger doses of prazosin significantly attenuated DDT-induced tremor and myoclonia and blocked both spinal and cortical alpha1 receptors, suggesting involvement of supraspinal, facilitative alpha1-mediated effects. These experiments support the hypotheses that the in vivo signs of tremor and myoclonus are related to DDT's actions at Na+ channels and involve polysynaptic transmission. Norepinephrine, acting at alpha1 receptors, may facilitate the intensity of the neurotoxic signs. This effect may be mediated by alpha1 receptors in several regions of the neuroaxis, rather than solely at the level of the spinal cord. This is the last report for this project; no further work is planned.
