Although classical and atypical antipsychotics may have different neurotoxic effects, their underlying mechanisms remain to be elucidated, especially regarding neuroglial function. In the present study, we compared the atypical antipsychotic risperidone (0.01-10 μM) with the typical antipsychotic haloperidol (0.01-10 μM) regarding different aspects such as glutamate uptake, glutamine synthetase (GS) activity, glutathione (GSH) content, and intracellular reactive oxygen species (ROS) production in C6 astroglial cells. Risperidone significantly increased glutamate uptake (up to 27%), GS activity (14%), and GSH content (up to 17%). In contrast, haloperidol was not able to change any of these glial functions. However, at concentration of 10 μM, haloperidol increased (12%) ROS production. Our data contribute to the clarification of different hypothesis concerning the putative neural responses after stimulus with different antipsychotics, and may establish important insights about how brain rewiring could be enhanced.