Anandamides: tolerance and cross-tolerance to delta 9-tetrahydrocannabinol.
In this study we examined whether tolerance develops to chronic exposure to anandamides [20:4, n-6 (ANA) and 20:3, n-6 (HLEA)] two of the recently discovered endogenous cannabinoid receptor ligands in brain. Tolerance to ANA and cross-tolerance to delta 9-tetrahydrocannabinol (delta 9-THC) was examined in female Sabra or C57BL/6 mice which had received daily injections (i.p.) of low (0.001-1 mg/kg) or high doses (20 mg/kg) of ANA or HLEA for 2 weeks. Twenty four h after the last injection, the mice were challenged with 20 mg/kg ANA or delta 9-THC. Animals were subjected to a series of tests frequently used to assess cannabinoid-induced effects. The results indicated that the high dose, but not the low doses of anandamides produced tolerance to ANA and cross-tolerance to delta 9-THC for motor activity in an open field, catalepsy on a ring, hypothermia and analgesia on a hot plate. One week after the last ANA treatment, tolerance was not present anymore. No tolerance to ANA was observed for reduced defecation in the open field, a measure of intestinal hypomotility. This phenomenon may possibly be attributed to a difference between activities produced through different types of cannabinoid receptors.
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Department of Natural Products, Hebrew University Medical Faculty, Jarusalem, Israel.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004361:Drug Tolerance; D063388:Endocannabinoids; D004983:Ethanolamines / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; D005231:Fatty Acids, Unsaturated; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C083631:homo-gamma-linolenylethanolamide; D013759:Dronabinol; C078814:anandamide