DDT is believed to produce hyperexcitability and tremor, beginning in the head region and progressing caudally with an increase in intensity. DDT produces these neurotoxic signs through actin at axonal sodium and potassium channels. The minimal anatomical structures required for the expression of DDT-induced tremor and myoclonus appears to be contained within the brainstem and spinal cord. Neurochemical changes occur which may be related to the repetitive neuronal firing induced by DDT. For example, increases in norepinephrine concentration has been found in brainstem as well as hypothalamus while a decrease in brainstem norepinephrine has been found in DDT-treated rats. These data suggest the NE neurotransmission mediated via alpha1 adrenoceptors may facilitate the expression of these signs. To further study the involvement of alpha1 adrenoceptors in DDT-induced motor function, male Fischer-344N rats were chronically implanted with an intrathecal cannula, and gavaged with p,p'-DDT or corn oil. Seven hours later animals were infused with vehicle and several doses of prazosin. Prazosin reduced the spectral profiles of spontaneous movements in control rats. Tremulous movements induced by DDT were unaffected by intrathecal prazosin at lower doses while higher doses significantly reduced the spectral profiles of rats pretreated with 45mg/kg DDT. Cortical and spinal tissues were used in ex vivo binding assays utilizing [3H]-prazosin binding sites, and produced a dose-related increase in cortical prazosin equivalents. These data indicate that while intrathecal prazosin will attenuate DDT-induced motor dysfunction, this effect requires blockade of alpha1 adrenoceptors in regions other than solely the spinal cord. This project was terminated as of June, 1989.
