Biogenic amines are important in the regulation of neuronal functions and complex behavior in the brain. However, putative contributions of glial cells to physiological effects of aminergic transmitters and their pathophysiological implications are poorly understood. Astrocytes are known to respond to dopamine (DA) with calcium transients that can be blocked by the D1- and D2-receptor subtype specific antagonists SCH23390 and Sulpiride. We demonstrate here that DA-sensitivity of cortical and striatal astrocytes is changed by application of either DA or epinephrine (EP), but not serotonin (5-HT). Exposure of cortical and striatal astroglial cultures for less than 1h to DA (> or = 10 micromol/l) or EP (> or = 1 micromol/l) leads to a significant reduction of astroglial DA-sensitivity. Whereas the DA-mediated downregulation of astroglial DA-sensitivity can be reverted by SCH23390 (> or = 1 micromol/l), and Sulpiride (> or = 10 micromol/l), EP-mediated effects are insensitive to these antagonists. In contrast to receptor function, expression of D1- and D2-DA-receptors is not altered by either DA or EP in cortical and striatal astroglial cells as revealed by western blot analysis. Our results demonstrate that sensitivity of astroglial cells to DA is modulated by DA and EP, adding new evidence to a role of astrocytes as targets for physiological and pathological effects of aminergic transmitters.