SELECTIVE EFFECTS OF THE ENDOGENOUS CANNABINOID ARACHIDONYLETHANOLAMIDE (ANANDAMIDE) ON REGIONAL CEREBRAL BLOOD-FLOW IN THE RAT

Recent biochemical data suggest that arachidonylethanolamide (AEA; ana ndamide) may be an endogenous ligand for brain cannabinoid receptors. The functional neuronal consequences of AEA binding to cannabinoid rec eptors are only poorly understood. Using regional cerebral blood flow (rCBF) as an indirect marker of neuronal activity, acute AEA administr ation dose-dependently depressed rCBF in unanesthetized rats. Although 3.0 mg/kg was ineffective in altering rCBF, 10 mg/kg led to a decreas e in rCBF in seven brain areas including the amygdala, cingulate,front al, prepyriform, sensorimotor, and claustrocortex. An additional 16 ar eas responded in a similar manner to AEA, but only after 30 mg/kg, inc luding the CAI and CA3 regions of the hippocampus, the rostral cove po rtion of the nucleus accumbens, and rostral caudate nucleus. Most of t hese rCBF effects dissipated between 15 and 20 min after drug administ ration, with only 4 regions, the basomedial and lateral amygdala, CA3 hippocampus and claustrocortex still depressed 60 min after an acute d rug injection. No significant changes in heart rate, blood pressure, o r blood gases were seen at the time of rCBF measurement, suggesting th at the observed drug effects were neuronally mediated. Taken together with existing behavioral data, these data support the hypothesis that an endogenous cannabinoid neural system exists in mammalian brain and may help to explain the unique behavioral profile seen after cannabino id administration. (C) 1998 American College of Neuropsychopharmacolog y. Published by Elsevier Science Inc.