EVALUATION OF CANNABIMIMETIC DISCRIMINATIVE STIMULUS EFFECTS OF ANANDAMIDE AND METHYLATED FLUOROANANDAMIDE IN RHESUS-MONKEYS

In previous research arachidonylethanolamide (anandamide) has been sho wn to produce behavioral effects in mice characteristic of psychoactiv e cannabinoids, including antinociception, catalepsy, hypothermia, and hypomotility. However, differences have also been found between anand amide and Delta(9)-tetrahy- drocannabinol (Delta(9)-THC), with anandam ide having lower potency, a more rapid onset, and shorter duration of action than Delta(9)-THC. Although it can produce Delta(9)-THC-like di scriminative stimulus effects in rats, anandamide also produces concom itant response rate decreasing effects, whereas with Delta(9)-THC ther e is a better separation of these two behavioral effects. The present study was designed to examine the discriminative stimulus effects of a nandamide in rhesus monkeys trained to discriminate Delta(9)-THC from vehicle. While anandamide failed to produce reliable substitution for Delta(9)-THC and did not reduce response rates at doses up to 10 mg/kg , 2-methylarachidonyl-2'-fluoroethylamide (methylated fluoroanadamide) , a putative stable analog of anandamide, produced full dose-dependent substitution for Delta(9)-THC at doses that caused no significant cha nges in response rates. These results suggest that systemically admini stered anandamide may be metabolized in monkeys before behaviorally ac tive concentrations could reach the brain and further suggest that the metabolically more stable analog of anandamide, methylated fluoroanan damide, may aid in the discovery of functional properties of the endog enous cannabinoid system. (C) 1997 Elsevier Science Inc.