Propofol inhibits long-term potentiation but not long-term depression in rat hippocampal slices.
BACKGROUND
Although propofol is known to produce amnesia when used for anesthesia, mechanisms underlying its effects on memory are poorly understood. The current study was designed to examine the effects of propofol on forms of synaptic plasticity thought to contribute to memory processing.


METHODS
Extracellular excitatory postsynaptic potentials were recorded from the CA1 region of rat hippocampal slices. Long-term potentiation (LTP) was induced using theta-burst stimulation (10 bursts of 4 pulses at 100 Hz, applied at 5 Hz) of the Schaffer-collateral pathway, while low-frequency stimulation (1 Hz x 900 pulses) was delivered to induce long-term depression. The authors also used higher-frequency stimulation (10 bursts of 4 pulses at 200 Hz, applied at 5 Hz) in the presence of MK-801 to examine the effects of propofol on an N-methyl-D-aspartate receptor-independent form of LTP.


RESULTS
At 30 microM, propofol inhibited LTP induction produced by theta-burst stimulation but had less effect on LTP maintenance. Similarly, when LTP was induced by 200-Hz stimulation in the presence of MK-801, propofol also blocked LTP induction. Propofol did not block LTP induction in the presence of picrotoxin, a specific antagonist of gamma-aminobutyric acid type A receptors, suggesting that modulation of gamma-aminobutyric acid type A receptors participates in propofol-mediated LTP inhibition. Propofol did not inhibit long-term depression.


CONCLUSIONS
Propofol inhibits LTP induction through modulation of gamma-aminobutyric acid type A receptors but not via inhibition of N-methyl-D-aspartate receptors. However, other factors also possibly contribute to propofol-mediated LTP inhibition.
Nagashima
Kimimoto
K
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Zorumski
Charles F
CF
Izumi
Yukitoshi
Y
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009473:Neuronal Plasticity; D015742:Propofol / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D015742:Propofol