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 A₁ receptor (A₁AR) 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 A₁AR in seasonal sensitization is unknown. In the current study, we characterize the A₁AR in the forebrain, hippocampus and hypothalamus of summer and torpid AGS. For the first time, we define the pharmacological characteristics of the A₁AR agonist, N⁶-cyclohexyladenosine and the A₁AR antagonist dipropylcyclopentylxanthine (DPCPX) in the AGS brain. In addition, we test the hypothesis that increased A₁AR agonist efficacy is responsible for sensitization of the A₁AR during the torpor season. The resulting ³⁵S-GTPγS binding data indicate an increase in agonist potency during torpor in two out of three brain regions. In addition to ³⁵S-GTPγS binding, [³H]DPCPX saturation and competition assays establish for the first-time pharmacological characteristics for the A₁AR agonist, N⁶-cyclohexyladenosine and the A₁AR antagonist dipropylcyclopentylxanthine (DPCPX) in AGS brain.