ANANDAMIDES - TOLERANCE AND CROSS-TOLERANCE TO DELTA(9)-TETRAHYDROCANNABINOL

In this study we examined whether tolerance develops to chronic exposu re to anandamides [20:4, n-6 (ANA) and 20:3, n-6 (HLEA)] two of the re cently discovered endogenous cannabinoid receptor ligands in brain. To lerance to ANA and cross-tolerance to Delta(9)-tetrahydrocannabinol (D elta(9)-THC) was examined in female Sabra or C57BL/6 mice which had re ceived daily injections (i.p.) of low (0.001-1 mg/kg) or high doses (2 0 mg/kg) of ANA or HLEA for 2 weeks. Twenty four h after the last inje ction, the mice were challenged with 20 mg/kg ANA or Delta(9)-THC. Ani mals were subjected to a series of tests frequently used to assess can nabinoid-induced effects. The results indicated that the high dose, bu t not the low doses of anandamides produced tolerance to ANA and cross -tolerance to Delta(9)-THC for motor activity in an open field, catale psy on a ring, hypothermia and analgesia on a hot plate. One week afte r the last ANA treatment, tolerance was not present anymore. No tolera nce to ANA was observed for reduced defecation in the open field, a me asure of intestinal hypomotility. This phenomenon may possibly be attr ibuted to a difference between activities produced through different t ypes of cannabinoid receptors.