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

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Abstract

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.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalEuropean Journal of Pharmacology
Volume272
Issue number1
DOIs
Publication statusPublished - 5 Jan 1995

Keywords

  • CANNABINOID
  • OPIOID
  • NORADRENALINE
  • BETA,GAMMA-METHYLENE-L-ATP
  • VAS DEFERENS, MOUSE
  • TOLERANCE
  • ADENOSINE 5'-TRIPHOSPHATE
  • SYMPATHETIC-NERVES
  • RECEPTOR-BINDING
  • GUINEA-PIG
  • DELTA-9-TETRAHYDROCANNABINOL
  • MORPHINE
  • BRAIN
  • cannabinoid
  • opioid
  • noradrenaline
  • ß,¿-Methylene- -ATP
  • Vas deferens mouse
  • tolerance

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