Delta9-tetrahydrocannabinol, but not the endogenous cannabinoid receptor ligand anandamide, produces conditioned place avoidance.

Although exogenous cannabinoid ligands such as delta9-tetrahydrocannabinol (THC) have been implicated in reward-related learning and aversion, the hedonic effects of the endogenous cannabinoid agonist anandamide (arachidonylethanolamide) have never been assessed. Thus, the effects of anandamide were tested in a place conditioning task. Male Wistar rats received THC (0.0-8.0 mg/kg) or anandamide (0.0-16.0 mg/kg) during conditioning sessions. The half-life of anandamide was increased by pretreatment with the protease inhibitor phenylmethylsulfonyl fluoride (2.0 mg/kg). A significant place aversion was found at the 1.0 and 1.5 mg/kg doses of THC. No significant place conditioning effects were found with anandamide. Locomotor activity during conditioning was significantly decreased by the 1.0, 1.5, 2.0 and 4.0 mg/kg doses of THC as well as the 8.0 and 16.0 mg/kg doses of anandamide. These results fail to implicate the endogenous cannabinoid anandamide in reward-related learning or aversion.