Aquaporin-4 knockout mice exhibit increased hypnotic susceptibility to ketamine.
PURPOSE
This study examines anesthetic/hypnotic effects of ketamine in AQP4 knockout (KO) and wild-type (WT) mice with the particular focus on neurotransmission.


MATERIALS AND METHODS
Ketamine (100 mg/kg) was intraperitoneally injected in 16 WT and 16 KO mice. The hypnotic potencies were evaluated by the loss of the righting reflex (LORR). The amino acids neurotransmitter levels in prefrontal cortex were measured by microdialysis.


RESULTS
This study demonstrated that AQP4 knockout significantly shortened the latency compared with WT mice (98.0 ± 4.2 vs. 138.1 ± 15.0 s, p < .05) and prolonged duration of LORR (884.7 ± 58.6 vs. 562.0 ± 51.7 s, p < .05) compared with WT mice in LORR induced by ketamine. Microdialysis showed that lack of AQP4 markedly decreased glutamate level within 20 min (p < .05) and increased γ-aminobutyric acid (GABA) level within 30-40 min (p < .05) after use of ketamine. Moreover, the levels of taurine were remarkably higher in KO mice than in WT mice, but no obvious differences in aspartate were observed between two genotypes.


CONCLUSION
AQP4 deficiency led to more susceptibility of mice to ketamine, which is probably due to the modulation of specific neurotransmitters, hinting an essential maintenance of synaptic activity mediated by AQP4 in the action of ketamine.
['Lv|Yunluo|Y|', 'Dai|Wangshu|W|0000-0002-9137-2998', 'Ge|Ai|A|', 'Fan|Yi|Y|', 'Hu|Gang|G|', 'Zeng|Yinming|Y|']
D000596:Amino Acids D000818:Animals D051401:Aquaporin 4 D018691:Excitatory Amino Acid Antagonists D006993:Hypnotics and Sedatives D007649:Ketamine D008297:Male D018345:Mice, Knockout D017551:Microdialysis D018377:Neurotransmitter Agents D017397:Prefrontal Cortex D057897:Reflex, Righting D005680:gamma-Aminobutyric Acid
aquaporin-4 ketamine loss of the righting reflex microdialysis synaptic transmission