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Neurotox Res. 2017 Nov;32(4):544-554. doi: 10.1007/s12640-017-9759-0. Epub 2017 Jun 2.

Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents.

Author information

1
Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego Street, 31-126, Kraków, Poland. nfpopik@cyf-kr.edu.pl.
2
Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland. nfpopik@cyf-kr.edu.pl.
3
Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
4
Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland. nowak@if-pan.krakow.pl.
5
Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Kraków, Poland. nowak@if-pan.krakow.pl.
6
Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Kraków, Poland.

Abstract

The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine (KET) produces rapid and sustained antidepressant effects in patients. Tiletamine (TIL; 2-ethylamino-2-thiophen-2-yl-cyclohexan-1-one) is another uncompetitive NMDA receptor antagonist, used in a medical (veterinary) setting as an anesthetic tranquilizer. Here, we compared the behavioral actions of KET and TIL in a variety of tests, focusing on antidepressant-like and dissociative-like effects in mice and rats. The minimum effective doses of KET and TIL were 10 mg/kg to reduce mouse forced swim test immobility and 15 mg/kg to reduce marble-burying behavior. However, at similar doses, both compounds diminished locomotor activity and disturbed learning processes in the mouse passive avoidance test and the rat novel object recognition test. KET and TIL also reduced social behavior and accompanying 50-kHz "happy" ultrasonic vocalizations (USVs) in rats. TIL (5-15 mg/kg) displayed additional anxiolytic-like effects in the four-plate test. Neither KET nor TIL affected pain response in the hot plate test. Examination of the "side effects" revealed that only at the highest doses investigated did both compounds produce motor deficits in the rotarod test in mice. While KET produced behavioral effects at doses comparable between species, in the rats, TIL was ~10 times more potent than in the mice. In summary, antidepressant-like properties of both KET and TIL are similar, as are their adverse effect liabilities. We suggest that TIL could be an alternative to KET as an antidepressant with an additional anxiolytic-like profile.

KEYWORDS:

Antidepressant-like effects; Ketamine; NMDA receptor; Tiletamine

PMID:
28577066
PMCID:
PMC5602060
DOI:
10.1007/s12640-017-9759-0
[Indexed for MEDLINE]
Free PMC Article

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