Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors. - Archive ouverte HAL Access content directly
Journal Articles Journal of Neuroscience Year : 2002

Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors.

(1) , (2) , (1)
1
2

Abstract

We have shown previously that the severity of handling-induced convulsions during ethanol withdrawal was reduced in A2A receptor knock-out (A2AR-/-) mice. In the present report, we further characterize the role of adenosine A(2A) receptors in ethanol consumption and neurobiological responses to this drug of abuse. Male A2AR-/- mice showed increased consumption of solutions containing 6 and 20% (v/v) ethanol compared with wild-type (A2AR+/+) control mice; female A2AR-/- mice showed increased consumption of solutions containing 6 and 10% ethanol. This slightly higher ethanol consumption was also related to increased ethanol preference. In contrast, A2AR-/- mice showed normal consumption of solutions containing either sucrose or quinine. Relative to A2AR+/+ mice, A2AR-/- mice were found to be less sensitive to the sedative effect of 3.0 gm/kg ethanol, as measured by more rapid recovery from ethanol-induced loss of righting reflex, and to the hypothermic effects of 1.5, 3.0, and 4.0 gm/kg ethanol, although plasma ethanol levels did not differ significantly between the two genotypes. The selective adenosine A2A receptor antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (10-30 mg/kg) significantly attenuated ethanol-induced (4.0 gm/kg) hypothermia in CD1 mice. To assess whether ethanol administration would induce differential tolerance in A2AR-/- and wild-type mice, we administered ethanol (3.0 gm/kg) over 4 consecutive days and found no difference in the development of tolerance; however, female A2AR-/- mice showed a lower tolerance-acquisition rate. These data suggest that activating the A2A receptors may play a role in suppressing alcohol-drinking behavior and is associated with the sensitivity to the intoxicating effects of acute ethanol administration.
Not file

Dates and versions

inserm-00746179 , version 1 (27-10-2012)

Identifiers

  • HAL Id : inserm-00746179 , version 1
  • PUBMED : 12451148

Cite

Mickaël Naassila, Catherine Ledent, Martine Daoust. Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors.. Journal of Neuroscience, 2002, 22 (23), pp.10487-93. ⟨inserm-00746179⟩
252 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More