Changes in rat brain energetic metabolism after exposure to anandamide or Delta(9)-tetrahydrocannabinol

The objective of this study was to investigate whether single and repeated administration of the cannabinoids anandamide or Delta(9)-tetrahydrocannabi nol affected brain energetic metabolism. Single administration of either an andamide (20 mg/kg) or Delta(9)-tetrahydrocannabinol (10 mg/kg) in rats ind uced a behaviour typical with cannabinoids. An increase in both brain mitoc hondria oxidative phosphorylation and cerebral lipoperoxidation was shown e x vivo. The cannabinoid CB1 receptor-specific antagonist, N-piperidino-5-(4 -chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141 716A; 3 mg/kg), reversed the anandamide-induced metabolic effects. Prolonge d exposure to anandamide (20 mg/kg, 16 days) induced behavioural tolerance and the disappearance of the increased mitochondria oxygen uptake and lipop eroxidation. Repeated Delta(9)-tetrahydrocannabinol injection (10 mg/kg, tw ice daily, 4.5 days) reduced brain metabolism and uncoupled respiration fro m oxidative phosphorylation. The present findings showed that both anandami de and Delta(9)-tetrahydrocannabinol enhanced the energetic brain metabolis m, probably via the cannabinoid CB1 receptor; the anandamide-tolerant brain of rats showed tolerance to the drug for metabolic effects, while the brai n of Delta(9)-tetrahydrocannabinol-tolerant rats showed metabolic signs of neuronal damage, i.e. low energy production. (C) 2000 Elsevier Science B.V. All rights reserved.