BIPHASIC EFFECTS OF ANANDAMIDE

Effects of the endogenous cannabimimetic anandamide were assessed over a wide dose range in a series of physiological and behavioral assays. These included the tetrad of tests in mice commonly used to assess ca nnabinoid-induced effects (motor activity, ring catalepsy, hypothermia , and analgesia tests), as well as a model for agonistic behavior on d yadic interactions of singly housed males with nonaggressive group-hou sed partners. Anandamide-induced effects on leukocyte phagocytosis wer e measured in a chemiluminescence assay. Results indicated that the hi gher doses tested (10-100 mg/kg) produced the well-known inhibitory ef fects in all of the above parameters as well as inhibition of phagocyt osis. The lowest dose of anandamide tested (0.01 mg/kg) stimulated beh avioral activities in the open field, on the ring and aggressive behav ior in timid singly housed mice. This dose of 0.01 mg/kg, also stimula ted phagocytosis. We suggest several possible mechanisms to explain th ese findings such as a differential involvement of a Gs and a Gi prote in activated at low and high doses, respectively, allosteric modulatio n of the cannabinoid, and activation of presynaptic cannabinoid recept ors by low doses of anandamide. (C) 1998 Elsevier Science Inc.