Rapid tolerance to behavioral effects of ethanol in rats: Prevention by R-(-)-ketamine.

Autor: Shafique H; Witkin Consulting Group, Carmel, IN, USA., Witkin JM; Witkin Consulting Group, Carmel, IN, USA; Perception Neuroscience Holdings, New York, NY, USA; Departments of Neuroscience and Trauma Research, Ascension St. Vincent Hospital, Indianapolis, IN, USA; Laboratory of Antiepileptic Drug Discovery, Peyton Manning Hospital for Children, Ascension St. Vincent, Indianapolis, IN, USA. Electronic address: witkinconsult@gmail.com., Smith JL; Laboratory of Antiepileptic Drug Discovery, Peyton Manning Hospital for Children, Ascension St. Vincent, Indianapolis, IN, USA., Kaniecki K; Perception Neuroscience Holdings, New York, NY, USA., Sporn J; Perception Neuroscience Holdings, New York, NY, USA., Holuj M; Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland., Krawczyk M; Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland., Kuziak A; Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland., Popik P; Behavioral Neuroscience and Drug Development, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2021 Apr; Vol. 203, pp. 173152. Date of Electronic Publication: 2021 Feb 10.
DOI: 10.1016/j.pbb.2021.173152
Abstrakt: R-(-)-ketamine has emerged as a potentially improved medication over that of the (S)-isomer (marketed as Spravato for depression). Recent data have suggested (R)-ketamine could have value in the treatment of substance use disorder. The present set of experiments was undertaken to examine whether (R)-ketamine might prevent tolerance development. Rapid ethanol (ETOH) tolerance was studied since racemic ketamine had previously been shown to block this tolerance development in rats. In the present study, male Sprague-Dawley rats were given two large doses of ETOH on Day 1 (2.3 + 1.7 g/kg) and 2.3 g/kg ETOH on Day 2. Animals were tested for effects of 2.3 g/kg ETOH on grip strength, inclined screen performance and rotarod performance on Day 1 with or without (R)-ketamine as a pretreatment. (R)-ketamine alone was tested at the highest dose studied (10 mg/kg) and did not significantly influence any dependent measure. (R)-ketamine (1-10 mg/kg) did not alter the acute effects of ETOH except for enhancing the effects of ETOH on the inclined screen test at 3 mg/kg. Between-subjects analysis documented that tolerance developed to the effects of ETOH only on the measure of grip strength. (R)-ketamine (3 mg/kg) given prior to ETOH on Day 1 exhibited a strong trend toward preventing tolerance development (p = 0.062). The present results extend prior findings on the potential value of (R)-ketamine in substance abuse disorder therapeutics and add to the literature on NMDA receptor blockade as a tolerance-regulating mechanism.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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