Medial temporal lobe epilepsy (MTLE) is a common cause of treatment-resistant seizures where excessive and hyper-synchronized neuronal activity is associated with reactive astrogliosis. Emerging evidence has indicated a role for neuron-astrocyte interactions in seizure activity. Previous studies have found increased astrocyte Ca2+ signals in mouse models for MTLE, but it has been difficult to disentangle how these drive or mitigate seizure activity in chronic epilepsy. We used an AAV8-GFAP-hM3Dq-mCherry vector to manipulate reactive astrocytes in the chronic phase of the mouse intrahippocampal kainic acid (IHKA) model. This vector drives the expression of a Gq coupled designer receptor exclusively activated by designer drugs (DREADDs) that increases Ca2+ transients in astrocytes. We controlled for non-specific effects using mice expressing the AAV8-GFAP-mCherry vector. We ascertained specific targeting of hippocampal astrocytes by immunohistochemistry and observed increased c-Fos expression specifically in hM3Dq transfected astrocytes of IHKA mice injected with the DREADD agonist CNO. Intriguingly, administration of CNO led to a slow decrease in seizure frequency that lasted up to one day in hM3Dq transfected IHKA mice but not in controls. This effect of astrocyte Gq DREADD activation was associated with a normalization of some measures of hippocampal energy metabolism and synaptic activity in IHKA mice. However, repeated daily injections of CNO led to a rebound in seizure frequency and a progressive increase in seizure duration in hM3Dq transfected IHKA mice. Consequentially, long-term activation of astrocyte Gq signalling did not improve anhedonia nor spatial memory function in the IHKA mouse model for epilepsy.