Involvement of the "peripheral" benzodiazepine receptor type (omega 3) in the tolerance to the electroencephalographic effects of benzodiazepines in rats: comparison of diazepam and clonazepam

Pharmacol Biochem Behav. 1990 Apr;35(4):933-6. doi: 10.1016/0091-3057(90)90381-q.


Rapid tolerance to the sedative effect of large doses of diazepam (10 mg/kg IV), but not of large doses of clonazepam (2 mg/kg IV) occurs in rats after 5 days of treatment on a once-a-day regimen. Electroencephalographic (EEG) studies show that such behavioral tolerance is associated with a decreased induction of spindle bursts and with an increased induction of 20-30 Hz waves (beta-like activity). Administration of clonazepam plus the agonist of the "peripheral" benzodiazepine receptor type (omega 3) Ro 5-4864 (4 mg/kg IV) for 5 days induces signs of behavioral and EEG tolerance to sedative effects of the benzodiazepine agonist. In animals treated for 5 days with diazepam plus the omega 3 antagonist PK 11195 (5 mg/kg IV), no signs of EEG and behavioral tolerance are observed. These results suggest that omega 3 type activation influences the development of rapid tolerance to the sedative effect of diazepam in rats.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology*
  • Clonazepam / pharmacology*
  • Diazepam / pharmacology*
  • Drug Tolerance / physiology
  • Electroencephalography / drug effects*
  • Isoquinolines / pharmacology*
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology*


  • Benzodiazepinones
  • Isoquinolines
  • Receptors, GABA-A
  • 4'-chlorodiazepam
  • Clonazepam
  • Diazepam
  • PK 11195