A preliminary investigation of the mechanisms underlying cannabinoid tolerance in the mouse vas deferens.
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.
Pertwee
R G
RG
Department of Biomedical Sciences, Marischal College, University of Aberdeen, Scotland, UK.
Griffin
G
G
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004361:Drug Tolerance; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D011957:Receptors, Opioid; C088155:methanandamide; D009020:Morphine; D013759:Dronabinol; D000255:Adenosine Triphosphate; C025351:delta(9)-tetrahydrocannabinolic acid; D003000:Clonidine; D009638:Norepinephrine