A preliminary investigation of the mechanisms underlying cannabinoid tolerance in the mouse vas deferens

Eur J Pharmacol. 1995 Jan 5;272(1):67-72. doi: 10.1016/0014-2999(94)00617-g.


Vasa deferentia taken from mice treated with delta 9-tetrahydrocannabinol (20 mg/kg i.p., once daily for 2 days) showed tolerance to the inhibitory effect of the cannabinoid, R-(+)-arachidonyl-1'-hydroxy-2'-propylamide, on electrically evoked twitches. This treatment did not induce tolerance to the inhibitory effects on the twitch response of morphine or clonidine or of selective mu-, delta- or kappa-opioid receptor agonists. Nor did it affect the contractile potencies of noradrenaline or beta,gamma-methylene-L-ATP. We suggest that cannabinoid tolerance in the vas deferens is attributable neither to downregulation of opioid receptors or alpha 2-adrenoceptors nor to an increased sensitivity of this tissue to its main contractile transmitters noradrenaline and ATP. A concentration of delta 9-tetrahydrocannabinol that inhibits electrically evoked twitches of the vas deferens (100 nM) did not alter the ability of noradrenaline or beta,gamma-methylene-L-ATP to induce contractions suggesting that delta 9-tetrahydrocannabinol inhibits the twitch response by acting prejunctionally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Arachidonic Acids / pharmacology
  • Clonidine / pharmacology
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Dronabinol / administration & dosage
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Drug Tolerance
  • Electric Stimulation
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Morphine / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Neuromuscular Junction / drug effects
  • Norepinephrine / pharmacology
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / metabolism
  • Vas Deferens / drug effects*
  • Vas Deferens / metabolism


  • Arachidonic Acids
  • Receptors, Opioid
  • methanandamide
  • Morphine
  • Dronabinol
  • Adenosine Triphosphate
  • delta(9)-tetrahydrocannabinolic acid
  • Clonidine
  • Norepinephrine