Novel adenosine analog, N6-(4-hydroxybenzyl)-adenosine, dampens alcohol drinking and seeking behaviors

Sa Ik Hong, Lee Peyton, Yijuang Chern, Doo Sup Choi

Research output: Contribution to journalArticle

Abstract

Adenosine signaling is associated with ethanol-related behaviors. We previously found that adenosine A2A receptor (A2AR) activation dampens ethanol drinking behaviors in equilibrative nucleoside transporter 1 (ENT1) knockout mice, and A2AR inhibition augments reward-seeking behavior in wild-type mice. The novel adenosine analog N6-(4-hydroxybenzyl)-adenosine (NHBA), which is isolated from the rhizomes of Gastrodia elata, activates A2AR and inhibits ENT1. Here, we examined the effects of NHBA on ethanol drinking in the two-bottle choice test and operant ethanol seeking behaviors. We selected mice exhibiting high ethanol drinking behavior in the two-bottle choice test. NHBA (0.1 mg/kg, i.p.) reduced ethanol drinking behavior in a limited-access 3-hour drinking session in high-consumption ethanol drinking mice, and NHBA (0.1 mg/kg, i.p.) did not alter locomotor activity in the open-field test. Operant conditioning with 10% ethanol and 10% sucrose (10E10S) reward increased zone entries and time spent in the ethanol zone, while NHBA (0.1 mg/kg, i.p.) dampened ethanol zone preference in the Y-maze. Furthermore, NHBA (0.1 mg/kg, i.p.) devalued 10E10S and 10% ethanol (10E) reward after operant conditioning with 10E10S and 10E. Taken together, NHBA through A2AR activation and ENT1 modulation may dampen ethanol drinking and seeking behaviors, suggesting that NHBA is a potential therapeutic agent for treating alcohol use disorder.

Original languageEnglish (US)
Pages (from-to)260-267
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume371
Issue number2
DOIs
StatePublished - Jan 1 2019

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Drinking Behavior
Alcohol Drinking
Adenosine
Ethanol
Equilibrative Nucleoside Transporter 1
Reward
Adenosine A2A Receptors
Drinking
Operant Conditioning
Sucrose
N6-(4-hydroxybenzyl)adenosine
Gastrodia
Rhizome
Locomotion
Knockout Mice

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Novel adenosine analog, N6-(4-hydroxybenzyl)-adenosine, dampens alcohol drinking and seeking behaviors. / Hong, Sa Ik; Peyton, Lee; Chern, Yijuang; Choi, Doo Sup.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 371, No. 2, 01.01.2019, p. 260-267.

Research output: Contribution to journalArticle

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