Propofol inhibits ketamine-induced c-fos expression in the rat posterior cingulate cortex.
Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has psychotomimetic activity. NMDA receptor antagonists cause morphological damage in the posterior cingulate cortex, which may be the brain region responsible for their psychotomimetic effects. Benzodiazepines are effective in preventing these effects through gamma-aminobutyric acid A (GABA(A)) receptor activation. We investigated the effect of propofol, which has both GABAA receptor-activating and NMDA receptor-suppressing activity, on ketamine-induced c-fos expression in the rat posterior cingulate cortex. Propofol or vehicle was continuously infused IV. Fifteen minutes later, 100 mg/kg ketamine or isotonic sodium chloride solution was injected intraperitoneally. Two hours later, brain sections were prepared, and c-fos expression was detected using immunohistochemical methods. Propofol significantly inhibited ketamine-induced c-fos expression in the posterior cingulate cortex. Propofol itself did not induce c-fos expression in this brain region. We conclude that propofol may be able to inhibit ketamine-induced psychotomimetic activity and neuronal damage.


CONCLUSIONS
In the present study, we demonstrated that the clinically relevant dose of propofol significantly inhibited ketamine-induced c-fos expression in the rat posterior cingulate cortex. This finding implies that propofol may inhibit ketamine-induced psychotomimetic activity and neuronal damage.
Nagata
A
A
Department of Anesthesiology, Kansai Medical University, Moriguchi, Osaka, Japan.
Nakao
S
S
Miyamoto
E
E
Inada
T
T
Tooyama
I
I
Kimura
H
H
Shingu
K
K
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D015742:Propofol / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D015742:Propofol