We have recently demonstrated that neonatal astrocytes derived from mice lacking beta-2 adrenergic receptors (β₂AR) possess higher proliferation rates, as compared to wild-type cells, an attribute that was shown to involve insulin-like growth factor (IGF) signaling. In the present study, we demonstrate that basal cAMP levels in β₂AR knockout astrocytes were significantly lower than in wild type cells. Furthermore, treatment with IGF-1 reduced intracellular cAMP levels in wild type astrocytes, yet had no effects on cAMP levels in β₂AR deficient astrocytes. Our data suggests that IGF-1 treatment influences cAMP production through a β₂AR-dependant mechanism in astrocytes. A deficit of β₂AR on astrocytes, as previously reported in multiple sclerosis, may influence cell proliferation, an action which could have implications in processes involved in astrogliosis.