The effect of ketamine isomers on both mice behavioral responses and c-Fos expression in the posterior cingulate and retrosplenial cortices.
Ketamine, a non-competitive NMDA receptor antagonist, is a racemic mixture. S(+) ketamine is presumed to be more potent as an anesthetic than R(-) ketamine, and causes less postanesthetic stimulation of locomotor activity than R(-) ketamine in animals at equihypnotic doses. In the present study, we investigated the effect of S(+), R(-), and racemic ketamines on mice behavioral responses and c-Fos expression in the posterior cingulate and retrosplenial cortices (PC/RS), which are suggested to be the brain regions responsible for NMDA-receptor-antagonist-induced psychotomimetic activity. Ataxia and head weaving and c-Fos expression in the PC/RS were significantly more induced by both S(+) and racemic ketamines than by R(-) ketamine at the same dose. S(+) ketamine induced significantly more potent ataxia than racemic ketamine at the same dose. Ketamine-induced c-Fos expression in the PC/RS correlated well with the intensity of behavioral responses. These results imply that R(-) ketamine is weaker than both S(+) and racemic ketamines in a psychotomimetic effect. Also, S(+) ketamine is more potent than racemic ketamine in a psychotomimetic effect and possibly in an anesthetic effect. They also indicate that PC/RS is at least one of the specific brain regions responsible for ketamine-induced behavioral responses in animals and a psychotomimetic activity in humans.
Nishizawa
N
N
Department of Anesthesiology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Japan.
Nakao
S
S
Nagata
A
A
Hirose
T
T
Masuzawa
M
M
Shingu
K
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006179:Gyrus Cinguli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007536:Isomerism; D007649:Ketamine / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism*; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D007649:Ketamine