Research reportBehavioral effects of fatty acid amide hydrolase inhibition on morphine withdrawal symptoms

Chronic morphine exposure causes tolerance and dependence. The cessation of morphine consumption induces a withdrawal syndrome that may involve cannabinoids and is characterized by undesirable psychological and physical signs. The present study examined whether augmentation of the endocannabinoid system by inhibition of fatty acid amide hydrolase could suppress the morphine withdrawal syndrome in morphine-addicted rats.Morphine dependency was induced by 7 consecutive days of morphine injection. The morphine-addicted rats received URB597 (1, 0.5, 0.3, 0.1, 0.03 mg/kg), a fatty acid amide hydrolase inhibitor, before the precipitation of morphine withdrawal syndromes by naloxone. Withdrawal symptoms including jumping, teeth chattering, paw tremor, wet dog shakes, face grooming, penis licking, standing, rearing, sniffing and percent of weight loss were recorded during 30 min after naloxone injection.The results showed that the morphine withdrawal precipitated rats had significantly more withdrawal symptoms than naive control rats and the administration of URB597 (all doses except 0.03 mg/kg) reduced most of the morphine withdrawal symptoms. We conclude that the administration of URB597 modulated morphine withdrawal symptoms. This finding shows that endocannabinoids interact with the opioid system during the morphine withdrawal period and that potentiation of the endogenous cannabinoid system by URB597 may be a new target strategy for the management of morphine addiction.

► Cannabinoid and opioid systems interact in morphine dependence. ► Effects of endocannabinoid augmentation on morphine withdrawal symptoms were examined.URB597 is an inhibitor of endocannabinoid, anandamide. ► Administration of URB597 reduced withdrawal symptoms. ► URB597 may consider as a new target strategy for the management of morphine addiction.