| First Author | Naassila M | Year | 2002 |
| Journal | J Neurosci | Volume | 22 |
| Issue | 23 | Pages | 10487-93 |
| PubMed ID | 12451148 | Mgi Jnum | J:80432 |
| Mgi Id | MGI:2445866 | Doi | 10.1523/JNEUROSCI.22-23-10487.2002 |
| Citation | Naassila M, et al. (2002) Low Ethanol Sensitivity and Increased Ethanol Consumption in Mice Lacking Adenosine A2A Receptors. J Neurosci 22(23):10487-93 |
| abstractText | We have shown previously that the severity of handling-induced convulsions during ethanol withdrawal was reduced in A(2A) receptor knock-out (A(2A)R(-/-)) 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 A(2A)R(-/-) mice showed increased consumption of solutions containing 6 and 20% (v/v) ethanol compared with wild-type (A(2A)R(+/+)) control mice; female A(2A)R(-/-) 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, A(2A)R(-/-) mice showed normal consumption of solutions containing either sucrose or quinine. Relative to A(2A)R(+/+) mice, A(2A)R(-/-) 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 A(2A) receptor antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]e thyl)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 A(2A)R(-/-) 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 A(2A)R(-/-) mice showed a lower tolerance-acquisition rate. These data suggest that activating the A(2A) receptors may play a role in suppressing alcohol-drinking behavior and is associated with the sensitivity to the intoxicating effects of acute ethanol administration. |
