Effects of a non-competitive N-methyl-d-aspartate (NMDA) antagonist, tiletamine, in adult zebrafish.
Tatiana O Kolesnikova, Sergey L Khatsko, Vadim A Shevyrin, Yuri Yu Morzherin, Allan V Kalueff
Neurotoxicology and teratology January 1, 2017 DOI: 10.1016/j.ntt.2016.11.009 via PubMed
Summary
AI-generated from the abstractTiletamine, a veterinary anesthetic related to ketamine, produces dose-dependent sedative effects in adult zebrafish. Immersion in 1 mg/L caused only reduced top entries in a novel tank test, while 5 and 10 mg/L caused robust sedation and skin darkening. Brain samples confirmed tiletamine presence only at the two higher doses. The results demonstrate potent neurotropic effects of tiletamine in zebrafish and support the use of fish-based aquatic screens for studying NMDA receptor antagonists.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult zebrafish (Danio rerio) |
| Intervention | Tiletamine |
| Dose | 1, 5 and 10 mg/L |
| Duration | 20-min immersion |
| Topics | Ketamine |
| Keywords | Aquatic screening Central glutamatergic system Sedative effects Tiletamine |
| Key finding | Tiletamine at 5 and 10 mg/L exerts robust dose-dependent sedative effects in zebrafish, while 1 mg/L produces only reduced top entries. |
Abstract
Tiletamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance in USA. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. However, the neurotropic profile of tiletamine remains poorly understood, necessitating novel models and in-vivo screens, including non-mammalian species. Zebrafish (Danio rerio) are rapidly becoming a popular model organism for screening various CNS drugs, including those acting at NMDA receptors. Here, we investigated acute behavioral effects of 1, 5 and 10mg/L of tiletamine on adult zebrafish. In the standard novel tank test, a 20-min immersion in 1mg/L of tiletamine produced no overt differences from control zebrafish (receiving 0.1% DMSO vehicle), except for reduced top entries. In contrast, tiletamine at 5 and 10mg/L exerted robust dose-dependent sedative effects in zebrafish (also darkening their skin coloration, similar to ketamine and PCP). Gas chromatography/mass spectrometry (GC/MS) analyses revealed no tiletamine peaks in control and 1mg/L groups, but detected tiletamine peaks in zebrafish brain samples at 5 and 10mg/L. Together, these findings demonstrate potent neurotropic effects of tiletamine in zebrafish, and their high sensitivity to this drug. Our findings also support the growing utility of fish-based aquatic screens for studying neuroactive properties of NMDA antagonists in-vivo.