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