PHYSIOLOGICAL AND BEHAVIORAL-EFFECTS OF THE ENDOGENOUS CANNABINOID, ARACHIDONYLETHANOLAMIDE (ANANDAMIDE), IN THE RAT

1 Arachidonylethanolamide (AEA; anandamide) has been isolated from mam malian brain and found to bind to, and is thought to be, an endogenous ligand for the cannabinoid receptor. In order to understand better it s behavioural and physiological properties, we have examined its acute effects in unanaesthetized freely behaving rats. 2 Intravenous AEA ca used dose-related decreases in locomotor behaviour, a pronounced hyper -reflexia, and a moderate antinociceptive state. At doses between 3 an d 30 mg kg(-1), a dose-dependent hypothermia and profound, time-depend ent cardiovascular changes were also observed. 3 An immediate bradycar dia exceeding 50% was seen within 10-15 s of administration and lasted up to 11 min following the highest dose of the drug. In contrast, the change in mean arterial pressure was biphasic: an immediate 20% decre ase in mean arterial pressure followed by a significant increase in bl ood pressure that lasted about 13 min after the highest dose. 4 These data demonstrate that AEA in the unanaesthetized rat exerts behavioura l and physiological effects generally similar to those seen following natural cannabinoids and synthetic cannabimimetic agents and suggests a role for AEA in regulation of various physiological processes.