Dual Effects of Anandamide on NMDA Receptor‐Mediated Responses and Neurotransmission

• Published in: Journal of neurochemistry 1998-02, Vol.70 (2), p.671-676
• Main Authors: Hampson, Aidan J., Bornheim, Lester M., Scanziani, Massimo, Yost, C. Spencer, Gray, Andrew T., Hansen, Bonnie M., Leonoudakis, Dmitri J., Bickler, Philip E.
• Format: Article
• Language: English
• Subjects: Anandamide; Animals; Arachidonic Acids - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - physiology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium channel ischemia; Cannabinoid; Cannabinoids - pharmacology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebellum - physiology; Cerebral Cortex - physiology; Dronabinol - pharmacology; Endocannabinoids; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Fundamental and applied biological sciences. Psychology; Glutamate; Hippocampus - physiology; In Vitro Techniques; Membrane Potentials - drug effects; Membrane Potentials - physiology; N-Methylaspartate - pharmacology; Neurons - drug effects; Neurons - physiology; NMDA; Oocytes - drug effects; Oocytes - physiology; Pertussis Toxin; Picrotoxin - pharmacology; Polyunsaturated Alkamides; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vertebrates: nervous system and sense organs; Virulence Factors, Bordetella - pharmacology; Wasp Venoms - pharmacology; Xenopus laevis
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.70020671.x

: Anandamide is an endogenous ligand of cannabinoid receptors that induces pharmacological responses in animals similar to those of cannabinoids such as Δ9‐tetrahydrocannabinol (THC). Typical pharmacological effects of cannabinoids include disruption of pain, memory formation, and motor coordination, systems that all depend on NMDA receptor mediated neurotransmission. We investigated whether anandamide can influence NMDA receptor activity by examining NMDA‐induced calcium flux (ΔCa2+NMDA) in rat brain slices. The presence of anandamide reduced ΔCa2+NMDA and the inhibition was disrupted by cannabinoid receptor antagonist, pertussis toxin treatment, and agatoxin (a calcium channel inhibitor). Whereas these treatments prevented anandamide inhibiting ΔCa2+NMDA, they also revealed another, underlying mechanism by which anandamide influences ΔCa2+NMDA. In the presence of cannabinoid receptor antagonist, anandamide potentiated ΔCa2+NMDA in cortical, cerebellar, and hippocampal slices. Anandamide (but not THC) also augmented NMDA‐stimulated currents in Xenopus oocytes expressing cloned NMDA receptors, suggesting a capacity to directly modulate NMDA receptor activity. In a similar manner, anandamide enhanced neurotransmission across NMDA receptor‐dependent synapses in hippocampus in a manner that was not mimicked by THC and was unaffected by cannabinoid receptor antagonist. These data demonstrate that anandamide can modulate NMDA receptor activity in addition to its role as a cannabinoid receptor ligand.