Dual Pathways Coupled to Oxytocin Molecular Signals in Cultured Astrocytes

Oxytocin's capacity to affect the glial cell functions is increasingly recognized. We previously reported that oxytocin could cause both excitation and inhibition of Ca²⁺ signals and glutamate release in the processes of adult rodent astrocytes. Our purpose here was to investigate oxytocin receptor expression and oxytocin effects in astrocytes. In primary cortical astrocytes, we assessed the presence of oxytocin receptors by confocal imaging, and the effects of oxytocin receptor activation on intracellular Ca²⁺ signals and glutamate release. We found that oxytocin receptors are expressed in both the soma and processes of astrocytes; oxytocin at nanomolar concentrations could induce dual responses in astrocytes, namely facilitation and inhibition of Ca²⁺ signals and glutamate release; the oxytocin facilitatory and inhibitory effects were duplicated by the biased agonists carbetocin and atosiban, respectively; and the facilitatory and the inhibitory effect were dependent on activation of a G_q and a G_i pathway, respectively. It is concluded that oxytocin effects in astrocytes could duplicate the effects in processes prepared from astrocytes matured in neuron-astrocyte networks, substantiating the use of astrocytes to study astrocytic oxytocin molecular signaling.