Premium
Dual Effects of Anandamide on NMDA Receptor‐Mediated Responses and Neurotransmission
Author(s) -
Hampson Aidan J.,
Bornheim Lester M.,
Scanziani Massimo,
Yost C. Spencer,
Gray Andrew T.,
Hansen Bonnie M.,
Leonoudakis Dmitri J.,
Bickler Philip E.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020671.x
Subject(s) - anandamide , cannabinoid receptor , nmda receptor , cannabinoid , depolarization induced suppression of inhibition , endocannabinoid system , chemistry , neurotransmission , pharmacology , neuroscience , biology , receptor , antagonist , biochemistry
Anandamide is an endogenous ligand of cannabinoid receptors that induces pharmacological responses in animals similar to those of cannabinoids such as Δ 9 ‐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 (ΔCa 2+ NMDA ) in rat brain slices. The presence of anandamide reduced ΔCa 2+ 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 ΔCa 2+ NMDA , they also revealed another, underlying mechanism by which anandamide influences ΔCa 2+ NMDA . In the presence of cannabinoid receptor antagonist, anandamide potentiated ΔCa 2+ 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.