Ketamine NMDA receptor-independent toxicity during zebrafish (Danio rerio) embryonic development

Developmental exposures to waterborne abused drugs alter physiological function and larval locomotion in early life stages of medaka fish

“…We demonstrated that embryonic exposure to environmentally relevant to micromolar levels of KET and MET delayed the heart rate and hatching time ( Figure 1) and increased the incidence of developmental abnormality (e.g., hemorrhage and defects in the eye and/or heart) ( Table S3, SI). Similarly, short exposures to super-anaesthetic doses of KET (low mM levels for ≤ 2 hr) decreased the heart rate of zebrafish embryos and caused prominent developmental abnormality in cardiac enlargement, cephalic disorders or tail/spine anomalies (Felix et al, 2014;Kanungo et al, 2012). The effect of KET on reducing the heart rate was reported for mammals, including humans, as well (Hotchkiss et al, 2007;Kim et al, 2007).…”

“…Although the maximum detected concentrations of these compounds are low (at the microgram per liter level in the hospital effluent and the nanogram per liter level in surface water), their ecotoxicologial risk to early life stages of aquatic organisms such as fish is significant, as we observed in the current study. Both KET and MET at the assessed concentrations had a minimal acute lethal effect on embryos and hatchlings (Table S2, SI); KET causes acute mortality at milligram to gram per liter levels in zebrafish embryos (Felix et al, 2014) and medaka larvae. To our knowledge, we first report on KET-and MET-induced alteration in developmental physiology (e.g., heart rate and hatching time) and swimming behavior (e.g., startle response and relative turn angle) at environmentally relevant concentrations of KET and MET.…”

“…Exposure to KET or MET confers a range of teratogenic effects or neurodevelopmental impact when administered in high doses and/or over prolonged periods during susceptible periods of development in rodents and other mammalian models (Brambrink et al, 2012;Scallet et al, 2004;Smith et al, 2003;Zou et al, 2009). Acute administration to KET at sub-and super-anesthetic doses (0.2-0.8 mg/mL for 20 min during the blastula stage) caused teratogenic effects in zebrafish embryos (Felix et al, 2014). Larvae of zebrafish exposed to KET (2.0 mM for 20 hr) adversely affected length and population of motor neuron and suppressed expression of neurogenic genes .…”

Zebrafish as a New Platform Used in Exploration of Ketamine-Induced Neurodevelopmental Toxicity

“…But after acridine orange (AO) staining, experimental groups, which were exposed to lower concentration of ketamine, showed no more cellular deaths than the control group [29][30][31]. However, exposure to higher concentration of ketamine will cause apoptosis in the region of thalamus and the connection part between midbrain and after brain.…”

Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach

“…KT for this study was the injectable medication containing ketamine hydrochloride (Dopalen®, Ceva). The concentrations of KT selected for this study were 5 mg.L -1 (n = 21 fish), 20 mg.L -1 (n = 17 fish), 40 mg.L -1 (n = 37 fish) and 60 mg.L -1 (n = 33 fish), based on previous studies [8,40,41]. The time of exposure of 20 min were selected according to previous studies on ketamine effects in adult zebrafish [8,40].…”