Blockade of only spinal alpha 1 adrenoceptors is insufficient to attenuate DDT-induced alterations in motor function.
Male Fischer 344N rats were chronically implanted with an intrathecal cannula and gavaged with p,p'-DDT (1,1,1-trichloro-2,2-bis[p-chlorophenyl]ethane; 30 or 45 mg/kg) or corn oil. Seven hours later, subjects were intrathecally infused with vehicle, 15, 30, 60, or 120 micrograms of prazosin (an alpha 1-adrenergic antagonist). Spectral analysis of bodily movements was performed 7.5, 8, and 10 hr after DDT administration. In control rats, 15 micrograms of prazosin reduced the spectral profiles of spontaneous movements. A 30-micrograms dose produced motor impairments, without significantly changing the spectral profiles. Tremulous movements induced by DDT were unaffected by 15 or 30 micrograms, whereas 60 or 120 micrograms of intrathecal prazosin significantly reduced the spectral profiles of rats pretreated with 45 mg/kg of DDT. Other subjects were administered vehicle or DDT (45 mg/kg), intrathecally infused with 15 or 60 micrograms of prazosin (7 hr), and sacrificed (7.5 hr). Noncannulated rats were gavaged with 60 mg/kg of DDT, injected subcutaneously (sc) with 0.5 mg/kg of prazosin (5.5 hr), and sacrificed (8 hr). Cortical and spinal tissues were used in ex vivo binding assay utilizing [3H]prazosin. Fifteen or sixty micrograms of intrathecal prazosin occupied similar percentages of spinal [3H]prazosin binding sites, but produced a dose-related increase in cortical prazosin equivalents. Sixty micrograms of intrathecal or 0.5 mg/kg of sc prazosin resulted in similar concentrations of cortical prazosin equivalents. Together, these data indicate that while intrathecal prazosin will attenuate DDT-induced motor dysfunction, this effect requires blockade of alpha 1 adrenoceptors in regions other than solely the spinal cord.
Herr
D W
DW
Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514.
Mailman
R B
RB
Tilson
H A
HA
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003634:DDT / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008297:Male; D009068:Movement / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014202:Tremor / Q000139:chemically induced / Q000503:physiopathology
D011942:Receptors, Adrenergic, alpha; D003634:DDT; D011224:Prazosin