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)-tetrahydrocannabinol affected brain energetic metabolism. Single administration of either anandamide (20 mg/kg) or Delta(9)-tetrahydrocannabinol (10 mg/kg) in rats induced a behaviour typical with cannabinoids. An increase in both brain mitochondria oxidative phosphorylation and cerebral lipoperoxidation was shown ex vivo. The cannabinoid CB(1) receptor-specific antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716A; 3 mg/kg), reversed the anandamide-induced metabolic effects. Prolonged exposure to anandamide (20 mg/kg, 16 days) induced behavioural tolerance and the disappearance of the increased mitochondria oxygen uptake and lipoperoxidation. Repeated Delta(9)-tetrahydrocannabinol injection (10 mg/kg, twice daily, 4.5 days) reduced brain metabolism and uncoupled respiration from oxidative phosphorylation. The present findings showed that both anandamide and Delta(9)-tetrahydrocannabinol enhanced the energetic brain metabolism, probably via the cannabinoid CB(1) receptor; the anandamide-tolerant brain of rats showed tolerance to the drug for metabolic effects, while the brain of Delta(9)-tetrahydrocannabinol-tolerant rats showed metabolic signs of neuronal damage, i.e. low energy production.
Costa
B
B
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, via Vanvitelli 32, 20129, Milan, Italy.
Colleoni
M
M
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids; D004734:Energy Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D008054:Lipid Peroxides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; D000077285:Rimonabant; C078814:anandamide