Abstract
PurposeThis study examines anesthetic/hypnotic effects of ketamine in AQP4 knockout (KO) and wild‐type (WT) mice with the particular focus on neurotransmission.Materials and MethodsKetamine (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.ResultsThis 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.
Highlights
General anesthesia is a medically induced state of unconsciousness with loss of protective reflexes and alternations of neurotransmitters, resulting from the administration of one or more general anesthetic agents (Jevtovic-Todorovic, 2016)
Our findings demonstrated that AQP4 knockout mice exhibited reduced latency and increased duration of loss of the righting reflex (LORR) after use of ketamine, suggesting that AQP4 plays an essential role in the susceptibility of mice to ketamine
As general anesthetic can benefit the patient through suppressing of excitatory neurotransmission (Jevtovic-Todorovic, 2016), our findings suggested that increased susceptibility to ketamine in KO mice might be ascribed to the lower levels of glutamate in the prefrontal cortex
Summary
General anesthesia is a medically induced state of unconsciousness with loss of protective reflexes and alternations of neurotransmitters, resulting from the administration of one or more general anesthetic agents (Jevtovic-Todorovic, 2016). Ketamine blocks nicotinic acetylcholine ion channels, increases dopaminergic. Glia express a large spectrum of neurotransmitter receptors and ionic channels to sense neuronal signals. They sense and respond to neuronal activity via sophisticated calcium and sodium signaling, which are considered to be involved in the modulation of anesthetic sensitivity (Liu et al, 2016). Astrocytes are crucial elements implicated in neuronal activity and express receptors for most neuroactive compounds. As the importance of astrocytes in neuronal activity, AQP4 has gained sufficient attraction for its roles in the regulation of astrocytic function, such as astroglial migration (Saadoun et al, 2005) and activation(Fan et al, 2008), K+ buffering (Padmawar, Yao, Bloch, Manley, & Verkman, 2005), as well as neurotransmission (Ding et al, 2007; Fan et al, 2005; Sun et al, 2007)
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