Blockade of only spinal α1 adrenoceptors is insufficient to attenuate DDT-induced alterations in motor function

D. W. Herr, R. B. Mailman, H. A. Tilson

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Abstract

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 μg of prazosin (an α1-adrenergic antagonist). Spectral analysis of bodily movements was performed 7.5, 8, and 10 hr after DDT administration. In control rats, 15 μg of prazosin reduced the spectral profiles of spontaneous movements. A 30-μg dose produced motor impairments, without significantly changing the spectral profiles. Tremulous movements induced by DDT were unaffected by 15 or 30 μg, whereas 60 or 120 μg 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 μg 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 assays 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 α1 adrenoceptors in regions other than solely the spinal cord.

Original languageEnglish (US)
Pages (from-to)11-26
Number of pages16
JournalToxicology and Applied Pharmacology
Volume101
Issue number1
DOIs
StatePublished - Oct 1989

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All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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