Low Ethanol Sensitivity and Increased Ethanol Consumption in Mice Lacking Adenosine A2AReceptors
Copyright policy )Low Ethanol Sensitivity and Increased Ethanol Consumption in Mice Lacking Adenosine A2AReceptors
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.
Male, Drug Resistance, Hypothermia, Choice Behavior, Mice, MESH: Behavior, Animal, MESH: Animals, Behavior, Animal, Sciences bio-médicales et agricoles, Animal -- drug effects, Purinergic P1 -- antagonists & inhibitors, Administration, MESH: Administration, Oral, MESH: Drug Resistance, Purinergic P1 -- deficiency, MESH: Receptor, Adenosine A2A, Oral, Purinergic P1 -- genetics, MESH: Ethanol, Alcohol Drinking, MESH: Reflex, Knockout, MESH: Drug Tolerance, MESH: Choice Behavior, Dose-Response Relationship, MESH: Sex Factors, Choice Behavior -- drug effects, Intraperitoneal, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Behavior, Dose-Response Relationship, Drug, Ethanol, MESH: Sucrose, Receptors, Purinergic P1, MESH: Triazoles, MESH: Female, MESH: Alcohol Drinking, Ethanol -- pharmacology, MESH: Body Temperature, MESH: Triazines, Administration, Oral, Drug Resistance -- genetics, MESH: Mice, Knockout, MESH: Dose-Response Relationship, Drug, Body Temperature, Reflex -- drug effects, MESH: Hypothermia, Receptors, Mice, Knockout, Quinine, Quinine -- pharmacology, Drug Tolerance, Hypothermia -- drug therapy, Alcohol Drinking -- genetics, Triazines -- pharmacology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Drug, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, Receptor, Body Temperature -- drug effects, MESH: Quinine, Receptor, Adenosine A2A, Injections, Adenosine A2A, Sex Factors, MESH: Purinergic P1 Receptor Antagonists, Animals, MESH: Receptors, Purinergic P1, Ethanol -- blood, MESH: Mice, [SDV.NEU] Life Sciences/Neurons and Cognition, Hypothermia -- chemically induced, MESH: Male, Purinergic P1 Receptor Antagonists, Sucrose -- pharmacology, Triazoles -- pharmacology, mesh: mesh:Quinine, mesh: mesh:Sex Factors, mesh: mesh:Body Temperature, mesh: mesh:Receptors, Purinergic P1, mesh: mesh:Receptor, Adenosine A2A, mesh: mesh:Administration, Oral, mesh: mesh:Female, mesh: mesh:Mice, Knockout, mesh: mesh:Behavior, Animal, mesh: mesh:Drug Resistance, mesh: mesh:Mice, mesh: mesh:Purinergic P1 Receptor Antagonists, mesh: mesh:Alcohol Drinking, mesh: mesh:Triazines, mesh: mesh:Reflex, mesh: mesh:Injections, Intraperitoneal, mesh: mesh:Ethanol, mesh: mesh:Drug Tolerance, mesh: mesh:Dose-Response Relationship, Drug, mesh: mesh:Hypothermia, mesh: mesh:Male, mesh: mesh:Animals, mesh: mesh:Choice Behavior, mesh: mesh:Triazoles, mesh: mesh:Sucrose
Male, Drug Resistance, Hypothermia, Choice Behavior, Mice, MESH: Behavior, Animal, MESH: Animals, Behavior, Animal, Sciences bio-médicales et agricoles, Animal -- drug effects, Purinergic P1 -- antagonists & inhibitors, Administration, MESH: Administration, Oral, MESH: Drug Resistance, Purinergic P1 -- deficiency, MESH: Receptor, Adenosine A2A, Oral, Purinergic P1 -- genetics, MESH: Ethanol, Alcohol Drinking, MESH: Reflex, Knockout, MESH: Drug Tolerance, MESH: Choice Behavior, Dose-Response Relationship, MESH: Sex Factors, Choice Behavior -- drug effects, Intraperitoneal, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Behavior, Dose-Response Relationship, Drug, Ethanol, MESH: Sucrose, Receptors, Purinergic P1, MESH: Triazoles, MESH: Female, MESH: Alcohol Drinking, Ethanol -- pharmacology, MESH: Body Temperature, MESH: Triazines, Administration, Oral, Drug Resistance -- genetics, MESH: Mice, Knockout, MESH: Dose-Response Relationship, Drug, Body Temperature, Reflex -- drug effects, MESH: Hypothermia, Receptors, Mice, Knockout, Quinine, Quinine -- pharmacology, Drug Tolerance, Hypothermia -- drug therapy, Alcohol Drinking -- genetics, Triazines -- pharmacology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Drug, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, Receptor, Body Temperature -- drug effects, MESH: Quinine, Receptor, Adenosine A2A, Injections, Adenosine A2A, Sex Factors, MESH: Purinergic P1 Receptor Antagonists, Animals, MESH: Receptors, Purinergic P1, Ethanol -- blood, MESH: Mice, [SDV.NEU] Life Sciences/Neurons and Cognition, Hypothermia -- chemically induced, MESH: Male, Purinergic P1 Receptor Antagonists, Sucrose -- pharmacology, Triazoles -- pharmacology, mesh: mesh:Quinine, mesh: mesh:Sex Factors, mesh: mesh:Body Temperature, mesh: mesh:Receptors, Purinergic P1, mesh: mesh:Receptor, Adenosine A2A, mesh: mesh:Administration, Oral, mesh: mesh:Female, mesh: mesh:Mice, Knockout, mesh: mesh:Behavior, Animal, mesh: mesh:Drug Resistance, mesh: mesh:Mice, mesh: mesh:Purinergic P1 Receptor Antagonists, mesh: mesh:Alcohol Drinking, mesh: mesh:Triazines, mesh: mesh:Reflex, mesh: mesh:Injections, Intraperitoneal, mesh: mesh:Ethanol, mesh: mesh:Drug Tolerance, mesh: mesh:Dose-Response Relationship, Drug, mesh: mesh:Hypothermia, mesh: mesh:Male, mesh: mesh:Animals, mesh: mesh:Choice Behavior, mesh: mesh:Triazoles, mesh: mesh:Sucrose
