Nitrous oxide (N2O) pre- and postsynaptically attenuates NMDA receptor-mediated neurotransmission in the amygdala.
The gaseous anaesthetic N(2)O displays analgesic, anxiolytic, and amnesic properties and has addictive psychedelic effects. N(2)O can further act as a neuroprotective agent, but may also become neurotoxic under certain conditions. Here, we employed whole-cell patch-clamp techniques in acute brain slices, and electrical afferent and infrared-guided laser stimulation to examine how N(2)O (65%) can affect NMDA receptor (NMDAR)-mediated synaptic transmission to principal neurons (PNs) of the adult murine basolateral amygdala (BLA). The BLA plays a critical role in anaesthetic-induced amnesia, the formation of aversive memories, as well as in fear and addictive behaviour. We evoked NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) in PNs of the BLA (BLA-PNs). We found these currents to be markedly decreased by N(2)O via pre- and postsynaptic actions: Without changing their kinetics and open probability, N(2)O impeded the voltage-dependent channel opening of NMDARs in BLA-PNs and diminished their unitary conductance as estimated by non-stationary fluctuation analysis. In addition, our data speak in favour of a N(2)O-produced reduction in the probability of glutamate release at the synapses generating the NMDAR-EPSCs. It is conceivable that these effects not only contribute to anaesthesia and anxiolysis, but also have bearings on learning and memory as well as excitotoxicity in the amygdala.
Ranft
Andreas
A
Klinische Neuropharmakologie, Max-Planck-Institut für Psychiatrie, München, Germany. a.ranft@lrz.tum.de
Kurz
Jörg
J
Becker
Klaus
K
Dodt
Hans-Ulrich
HU
Zieglgänsberger
Walter
W
Rammes
Gerhard
G
Kochs
Eberhard
E
Eder
Matthias
M
D000679:Amygdala / Q000166:cytology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D007834:Lasers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009609:Nitrous Oxide / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
C102508:(carboxy-2-nitrobenzyl)glutamic acid; D018712:Analgesics, Non-Narcotic; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D009609:Nitrous Oxide; D010100:Oxygen