Centrally administered oligodeoxynucleotides in rats: occurrence of non-specific effects

B Schöbitz, G Pezeshki, J C Probst, J M Reul, T Skutella, T Stöhr, F Holsboer, R Spanagel

Research output: Contribution to journalArticle (Academic Journal)peer-review

42 Citations (Scopus)

Abstract

We studied the effects of various intracerebroventricularly administered oligodeoxynucleotides on body temperature, locomotor activity, food intake and water consumption in rats during a 24 h period with a radio-telemetric system. Both complete phosphorothioate oligodeoxynucleotides and end-inverted oligodeoxynucleotides dose-dependently elevated body temperature, suppressed food and fluid intake and inhibited nighttime activity. Apparently these effects do not depend on the nucleotide sequence because antisense and sense arginine vasopressin and oxytocin oligodeoxynucleotides, as well as a missense oligodeoxynucleotide produced comparable changes in the autonomous and behavioral parameters. In control experiments neither contaminants from the chemical synthesis nor endotoxins produced such effects, whereas native DNA from salmon sperm did. Fever and sickness-like behavior in response to missense phosphorothioate oligodeoxynucleotides were accompanied by elevated concentrations of circulating corticosterone and by a marked increase in interleukin 6 mRNA in brain and spleen, indicating that centrally administered oligodeoxynucleotides stimulate the production of pyrogenic inflammatory mediators in both central nervous system and peripheral tissues. Our results indicate that centrally administered oligodeoxynucleotides produce beside their intended sequence-specific effects also transient and sequence-independent effects due to their nucleic acid structure.

Original languageEnglish
Pages (from-to)97-107
Number of pages11
JournalEuropean Journal of Pharmacology
Volume331
Issue number2-3
Publication statusPublished - 23 Jul 1997

Keywords

  • Animals
  • Behavior, Animal
  • Blotting, Northern
  • Body Temperature
  • Corticosterone
  • DNA
  • Dose-Response Relationship, Drug
  • Drinking
  • Eating
  • Endotoxins
  • Injections, Intraventricular
  • Interleukin-6
  • Male
  • Motor Activity
  • Oligonucleotides
  • Rats
  • Rats, Wistar

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