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Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors
- Source :
- Journal of Neuroscience, Journal of Neuroscience, 2002, 22 (23), pp.10487-93, Journal of Neuroscience, Society for Neuroscience, 2002, 22 (23), pp.10487-93
- Publication Year :
- 2002
- Publisher :
- HAL CCSD, 2002.
-
Abstract
- 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]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 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.
- Subjects :
- Male
Sucrose
MESH: Body Temperature
MESH: Triazines
Drug Resistance
Adenosine A2A receptor
Administration, Oral
Hypothermia
Choice Behavior
MESH: Mice, Knockout
Body Temperature
MESH: Dose-Response Relationship, Drug
chemistry.chemical_compound
Mice
0302 clinical medicine
MESH: Hypothermia
MESH: Behavior, Animal
MESH: Animals
Receptor
Mice, Knockout
0303 health sciences
Quinine
Behavior, Animal
Triazines
General Neuroscience
Drug Tolerance
3. Good health
Biochemistry
Adenosine a
MESH: Administration, Oral
MESH: Drug Resistance
MESH: Receptor, Adenosine A2A
Female
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
medicine.symptom
Injections, Intraperitoneal
MESH: Injections, Intraperitoneal
medicine.drug
medicine.medical_specialty
MESH: Ethanol
Alcohol Drinking
Receptor, Adenosine A2A
MESH: Quinine
MESH: Reflex
MESH: Drug Tolerance
MESH: Choice Behavior
03 medical and health sciences
Sex Factors
MESH: Sex Factors
MESH: Purinergic P1 Receptor Antagonists
Internal medicine
Reflex
medicine
Animals
MESH: Receptors, Purinergic P1
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
ARTICLE
MESH: Mice
030304 developmental biology
Ethanol
Dose-Response Relationship, Drug
MESH: Sucrose
Antagonist
Receptors, Purinergic P1
Triazoles
MESH: Male
Endocrinology
chemistry
Purinergic P1 Receptor Antagonists
MESH: Triazoles
MESH: Female
030217 neurology & neurosurgery
MESH: Alcohol Drinking
Subjects
Details
- Language :
- English
- ISSN :
- 02706474 and 15292401
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience, Journal of Neuroscience, 2002, 22 (23), pp.10487-93, Journal of Neuroscience, Society for Neuroscience, 2002, 22 (23), pp.10487-93
- Accession number :
- edsair.doi.dedup.....c21e33c62676261d734079422ce67782