ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in cognitive flexibility induced by withdrawal from 'binge-like' ethanol exposure in rats
PBN-AR
Instytucja
Wydział Inżynierii Materiałowej i Ceramiki (Akademia Górniczo-Hutnicza im. Stanisława Staszica w Krakowie)
Informacje podstawowe
Główny język publikacji
EN
Czasopismo
Behavioural Brain Research (30pkt w roku publikacji)
ISSN
0166-4328
EISSN
1872-7549
Wydawca
Elsevier Science BV
DOI
Rok publikacji
2018
Numer zeszytu
Strony od-do
9--16
Numer tomu
338
Link do pełnego tekstu
Identyfikator DOI
Liczba arkuszy
0.6
Autorzy
(liczba autorów: 10)
Pozostali autorzy
+ 8
Słowa kluczowe
EN
NMDA receptor
ethanol
barnes maze
reversal learning
mGlu5 receptor
Streszczenia
Język
EN
Treść
Repeated exposure to and withdrawal from ethanol induces deficits in spatial reversal learning. Data indicate that metabotropic glutamate 5 (mGlu5) receptors are implicated in synaptic plasticity and learning and memory. These receptors functionally interact with N-methyl-d-aspartate (NMDA) receptors, and activation of one type results in the activation of the other. We examined whether (S)-(4-fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl (ADX-47273), a positive allosteric modulator (PAM) of mGlu5 receptor, attenuates deficits in reversal learning induced by withdrawal (11-13 days) from ‘binge-like’ ethanol input (5.0 g/kg, i.g. for 5 days) in the Barnes maze (a spatial learning) task in rats. We additionally examined the effects of ADX-47273 on the expression of the NMDA receptors subunit, GluN2B, in the hippocampus and prefrontal cortex, on the 13th day of ethanol withdrawal. Herein, withdrawal from repeated ethanol administration impaired reversal learning, but not the probe trial. Moreover, ADX-47273 (30 mg/kg, i.p.) given prior to the first reversal learning trial for 3 days in the Barnes maze, significantly enhanced performance in the ethanol-treated group. The 13th day of ethanol abstinence decreased the expression of the GluN2 B subunit in the selected brain regions, but ADX-47273 administration increased it. In conclusion, positive allosteric modulation of mGlu5 receptors recovered spatial reversal learning impairment induced by withdrawal from ‘binge-like’ ethanol exposure. Such effect seems to be correlated with the mGlu5 receptors mediated potentiation of GluN2B-NMDA receptor mediated responses in the hippocampus and prefrontal cortex. Thus, our results emphasize the role of mGlu5 receptor PAM in the adaptive learning impaired by ethanol exposure.
Cechy publikacji
original article
peer-reviewed
Inne
System-identifier
idp:109698
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