Endocannabinoids restrict hippocampal long-term potentiation via CB1.
Cannabinoid ligands alter cognition and prevent long-term potentiation (LTP) of synaptic transmission, but the influence of endogenously formed cannabinoids (eCBs) on hippocampal LTP remains ambiguous. In the accompanying study, we showed that eCB levels regulated by cyclooxygenase-2 (COX-2) tonically decrease basal excitatory transmission. Here, we investigated the influence of eCBs on LTP in CA1 hippocampus. LTP elicited by moderate stimulations (20 or 50 pulses) was facilitated in slices treated with a CB1 antagonist, whereas LTP elicited with robust stimulations (100 or 200 pulses) was unchanged by CB1 blockade. LTP elicited with theta-burst stimulations also was facilitated with CB1 blockade, revealing a tonic inhibitory influence of eCBs on LTP induction. Conversely, inhibition of COX-2 prevented LTP elicited with theta burst stimulations. Inhibition of COX-1 or other routes of eCB degradation did not affect LTP. We conclude that COX-2 regulates the formation of CB1 ligands that negatively regulate LTP.
Slanina
Kristen A
KA
Department of Neuropharmacology, CVN 12, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Roberto
Marisa
M
Schweitzer
Paul
P
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D063388:Endocannabinoids; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D000077239:Meloxicam; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects*; D013826:Theta Rhythm; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D063385:Cannabinoid Receptor Modulators; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000077239:Meloxicam