Development of behavioral tolerance to delta 9-THC without alteration of cannabinoid receptor binding or mRNA levels in whole brain

Pharmacol Biochem Behav. 1993 Nov;46(3):575-9. doi: 10.1016/0091-3057(93)90546-6.


The effect of repetitive administration of delta-9-tetrahydrocannabinol (delta 9-THC) in mice on behavioral and biochemical tolerance was determined in this study. Mice were injected twice daily with 10 mg/kg delta 9-THC for 6.5 days. On day 8, spontaneous activity was assessed or whole-brain homogenates were prepared for the cannabinoid receptor binding and mRNA studies. Although a twenty-sevenfold tolerance to delta 9-THC was observed in the behavioral assay, there was no significant alteration in receptor binding or mRNA levels.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Blotting, Northern
  • Brain Chemistry / drug effects*
  • Cyclohexanols / pharmacology
  • DNA Probes
  • Dronabinol / pharmacology*
  • Drug Tolerance
  • Electrophoresis, Polyacrylamide Gel
  • In Situ Hybridization
  • In Vitro Techniques
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Mice
  • Mice, Inbred ICR
  • RNA, Messenger / biosynthesis*
  • Receptors, Cannabinoid
  • Receptors, Drug / drug effects*
  • Receptors, Drug / metabolism


  • Cyclohexanols
  • DNA Probes
  • RNA, Messenger
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol