Characterization and Seasonal Modulation of Adenosine A1 Receptors in the Arctic Ground Squirrel Brain

Hibernation is an adaptation that allows animals such as the Arctic ground squirrel (AGS) to survive the absence of food or water during the winter season. Understanding mechanisms of metabolic suppression during hibernation torpor promises new therapies for critical care. The activation of the Adenosine A(1) receptor (A(1)AR) has been shown to be necessary and sufficient for entrance into hibernation with a winter season sensitization to the agonist, but the role of the A(1)AR in seasonal sensitization is unknown. In the current study, we characterize the A(1)AR in the forebrain, hippocampus and hypothalamus of summer and torpid AGS. For the first time, we define the pharmacological characteristics of the A(1)AR agonist, N-6-cyclohexyladenosine and the A(1)AR antagonist dipropylcyclopentylxanthine (DPCPX) in the AGS brain. In addition, we test the hypothesis that increased A(1)AR agonist efficacy is responsible for sensitization of the A(1)AR during the torpor season. The resulting S-35-GTP gamma S binding data indicate an increase in agonist potency during torpor in two out of three brain regions. In addition to S-35-GTP gamma S binding, [H-3]DPCPX saturation and competition assays establish for the first-time pharmacological characteristics for the A(1)AR agonist, N-6-cyclohexyladenosine and the A(1)AR antagonist dipropylcyclopentylxanthine (DPCPX) in AGS brain.