BACKGROUND: Cellular target sites and the neurochemical compounds responsible for anesthetic action remain unclear. This study was designed to detect regional changes in neurochemical compounds by NMR spectroscopy of extracted rabbit brain tissue after anesthetizing with thiopental or ketamine.

METHODS: Nine healthy white New Zealand rabbits (2.5-3.0 kg) were studied. A marginal ear vein was punctured for continuous intravenous infusion. Controlled breathing was maintained using a Jackson-Ree circuit after intubation during thiopental (n = 3) or ketamine (n = 3) anesthesia. After maintaining anesthesia for 30 minutes, brains were extracted and placed in liquid nitrogen. Rabbits in the control group (n = 3) were sacrificed using KCl and processed in the same manner. Extracted brain tissues were divided into frontal lobe, temporal lobe, occipital lobe, parietal lobe, pons, midbrain, basal ganglia and spinal cord. The ¹H-NMR spectra of extracted regional brain tissues were obtained, and neurochemical compounds such as gamma-aminobutyric acid (GABA), N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine (Cr) were compared with those of normal control tissues.

RESULTS: In the thiopental group, the GABA/Cr and NAA/Cr ratios of brain regions were not significantly different from those of the control group. The Cho/Cr ratios of the frontal lobe, parietal lobe, and basal ganglia were significantly higher than those of the control group. In the ketamine group, the GABA/Cr ratio of the midbrain was significantly lower than that of the control group. However, Cho/Cr ratios of the parietal lobe, temporal lobe, and midbrain were significantly higher than those of the control group, though the NAA/Cr ratio was similar to that of the control.

CONCLUSIONS: These results suggest that the anesthetic actions of thiopental, such as, its sedative and hypnotic effects are due to increased GABA activity. Inhibition of acetylcholine induced neurotransmission was observed particularly in the frontal lobe, parietal lobe, and basal ganglia in thiopental anesthesia and in the parietal lobe, temporal lobe and midbrain in ketamine anesthesia. Neurotoxicity was not observed for either drug in anesthetized brain tissue.