N-oleoyl-dopamine increases locomotor activity in the rat

N-oleoyl-dopamine (OLDA), a condensation product of oleic acid and dopamine (DA), is a bioactive lipid whose biological functions are not yet fully explored. The compound crosses the blood-brain barrier and might be considered as a carrier of DA into the brain. In this study we sought to determine whether OLDA would influence locomotor behavior and whether the central DA system would be involved in such influence. We addressed this issue by investigating horizontal locomotor activity in male Wistar rats after intraperitoneal administration of OLDA, 5-20 mg/kg, before and after pre-treatment with haloperidol, a D2 receptor antagonist. We found that OLDA caused a prompt stimulation of locomotor activity, with a bell-shaped dose-response. The maximum stimulatory effect was observed after 10 mg/kg of OLDA where the mean distance traveled by rats during a 2-hour test increased to 1213+/-196(SE) cm from the 403+/-89 cm in the vehicle-treated rats (P<0.05). This effect was dose-dependently antagonized by haloperidol (0.1-0.2 mg/kg). The results support the hypothesis that the OLDA-induced hyperlocomotion was mediated by the stimulation of DA systems. Using in vitro assays, we further demonstrated that OLDA is a stable compound that resists hydrolysis over a 2-hour period and thus the integral OLDA compound exerted DA-like effects. We conclude that OLDA is a potential brain modifier of motor behavior, the biological consequences of which remain to be explored.