@conference{
author = "Stanković, Tamara and Batinić, Bojan and Santrač, Anja and Marković, Bojan and Drobac, Milica and Arsenijević, Jelena and Savić, Miroslav",
year = "2018",
abstract = "Cilj ove studije bio je da se ispita da li akutni tretman ligandom XHe‐III‐74, novim
pozitivnim modulatorom α4‐GABAA receptora, može smanjiti unos alkohola u mišijem
modelu „pijenja u mraku” (eng. drinking in the dark – DID).
Eksperimenti su sprovedeni na odraslim miševima soja C57BL/6. Moguće
sedativno dejstvo XHe‐III‐74 (0,5; 2 ili 5 mg/kg, i.p.) ispitano je u testu spontane
lokomotorne aktivnosti (SLA). Prvog dana jednog ciklusa DID eksperimenta svaka
životinja imala je dvočasovni pristup alkoholu (etanol 20%, v/v). Drugog dana tretman
je primenjivan 20 minuta pre pristupa alkoholu, a trećeg dana pacovi nisu tretirani
ničim. U svim DID eksperimentima svaka životinja je prošla kroz četiri ciklusa tako da je
u svakom primila jednu od tri doze tretmana ili placebo. U prvom DID eksperimentu
testirali smo efekat XHe‐III‐74 (0,8; 2 ili 5 mg/kg) na unos vode (n=12, po dozi), dok
smo u drugom testirali efekat istih doza na unos alkohola (n=14). Ekekat referetnog
leka, naltreksona (1; 4 ili 16 mg/kg) testiran je u trećem eksperimentu.
U SLA testu, nijedna od odabranih doza XHe‐III‐74 nije smanjila pređeni put životinje
(F3,20=0,48; p=0,703). U prvom DID eksperiementu, tretman XHe‐III‐74 nije uticao na
unos vode (F3,33=0,39; p=0,763). Unos alkohola, meren u drugom DID eksperimentu,
izmenjen je pod dejstvom XHe‐III‐74 tretmana (F3,39=7,41; p<0,001), gde je doza XHe‐
III‐74 od 5 mg/kg značajno smanjila unos u poređenju sa kontrolom (p<0,001). U
trećem eksperimentu, naltrekson je značajno smanjio unos alkohola (F60,3=22.18;
p<0,001), i to u sve tri doze: 1 mg/kg (p<0,001); 4 mg/kg (p<0,001) i 16 mg/kg
(p<0,001).
Uz očekivani izostanak sedativnog dejstva, XHe‐III‐74, pozitivni modulator α4‐
GABAA receptora, ispoljio je evidentan potencijal za smanjenje unosa alkohola u
mišijem DID modelu, koji se može porediti sa onim postignutim primenom naltreksona,
referentnog leka u terapiji poremećaja unosa alkohola., The present study aimed to investigate whether acute treatment with XHe‐III‐74,
a novel positive modulator of α4‐GABAA receptors, may reduce alcohol intake in mouse
model of „drinking in the dark” (DID).
All experiments were conducted on adult C57BL/6 mice. Potential sedative
properties of XHe‐III‐74, (0.5, 2 or 5 mg/kg, i.p.) were assessed using spontaneous
locomotor activity (SLA) test. On the 1st day of one DID cycle each animal had 2‐h access
to ethanol (20%, v/v), on the 2nd day treatment was given 20 min before the access to
ethanol, while on the 3rd day the animal was not treated in any way. In all DID
experiments each animal passed through four cycles and respectively receive one of
three treatment doses or solvent in each cycle. In Experiment 1 we tested whether XHe‐
III‐74 (0.8, 2 or 5 mg/kg) had any effects on water intake (n=12 per treatment dose),
while in Experiment 2, the same doses were used to test potential decrease of ethanol
intake (n=14). Effects of the reference drug, naltrexone (1; 4 and 16 mg/kg) were
tested in Experiment 3 (n=21). In the SLA test, none of the selected XHe‐III‐74 doses
decreased the distance traveled (F3,20=0.48; p=0.703). In DID Experiment 1, XHe‐III‐74
treatment didn’t affect water intake (F33,3=0.39; p=0.763). Ethanol intake, measured in
Experiment 2, was affected by XHe‐III‐74 treatment (F39,3=7.41; p<0.001), with 5 mg/kg
XHe‐III‐74 significantly reducing the intake relative to control (p<0.001). In Experiment
3, naltrexone significantly affected the intake of ethanol (F60,3=22.18; p<0.001), with all
three doses reducing the intake: 1 mg/kg (p<0.001); 4 mg/kg (p<0.001) and 16 mg/kg
(p<0.001).
With expected lack of sedative actions, XHe‐III‐74, a positive modulator of α4‐
GABAARs, exhibited a clear potential for decreasing ethanol intake in mouse DID model,
comparable to that of naltrexone, a reference drug in alcohol use disorder.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Novi pozitivni modulator α4-GABAA receptora, XHE-III-74, smanjuje unos alkohola u mišijem modelu "pijenja u mraku", A novel positive modulator of α4‐GABAA receptors, XHE-III‐74, reduces ethanol intake in mouse „drinking in the dark” model",
volume = "68",
number = "3",
pages = "664-665",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5284"
}
