Selective effects of the endogenous cannabinoid arachidonylethanolamide (anandamide) on regional cerebral blood flow in the rat.
Recent biochemical data suggest that arachidonylethanolamide (AEA; anandamide) may be an endogenous ligand for brain cannabinoid receptors. The functional neuronal consequences of AEA binding to cannabinoid receptors are only poorly understood. Using regional cerebral blood flow (rCBF) as an indirect marker of neuronal activity, acute AEA administration dose-dependently depressed rCBF in unanesthetized rats. Although 3.0 mg/kg was ineffective in altering rCBF, 10 mg/kg led to a decrease in rCBF in seven brain areas including the amygdala, cingulate, frontal, prepyriform, sensorimotor, and claustrocortex. An additional 16 areas responded in a similar manner to AEA, but only after 30 mg/kg, including the CA1 and CA3 regions of the hippocampus, the rostral core portion of the nucleus accumbens, and rostral caudate nucleus. Most of these rCBF effects dissipated between 15 and 20 min after drug administration, with only 4 regions, the basomedial and lateral amygdala, CA3 hippocampus and claustrocortex still depressed 60 min after an acute drug injection. No significant changes in heart rate, blood pressure, or blood gases were seen at the time of rCBF measurement, suggesting that 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 cannabinoid administration.
Stein
E A
EA
Department of Psychiatry, Medical College of Wisconsin, Milwaukee 53226, USA.
Fuller
S A
SA
Edgemond
W S
WS
Campbell
W B
WB
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001345:Autoradiography; D001784:Blood Gas Analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D063388:Endocannabinoids; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D053284:Polyunsaturated Alkamides; D051381:Rats; D017207:Rats, Sprague-Dawley
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide