INTRODUCTION: Exposure to drugs of abuse initiates molecular alterations in the central nervous system that lead to an increased overall tenderness to addiction with subsequent drug exposures. These drug-induced alterations employ changes in gene expression, which may underlie the behavioral aberrancy that define a state of addiction. AIM(S): To identify the specific transcriptional alterations in different stages of morphine addiction in the hippocampus (Hip), brain region which play a role in the acquisition and extinction of memories associated with drug seeking behavior. METHOD(S): C57BL/6J male mice were injected twice daily for 3 weeks with morphine (increasing doses, 20-100 mg/kg i.p.). Animals were observed for spontaneous signs of withdrawal and behavior was measured in first and third week of abstinence. Morphine induced gene expression in the Hip was analyzed, using the qPCR technology. RESULTS: 24 h after chronic treatment we have observed spontaneous withdrawal syndrome and the peak of corticosterone levels in blood. Morphine-abstinent mice exhibited a variety of depression-like behaviors and cognitive deficits. Analyzes of Hip transcriptional responses to morphine indicated that most of genes regulated by morphine injection are GR-dependent, with a number of them being astrocyte‑specific (Gjb6, Plin4, Slc1a3, Gfap, Gja1). Analyzed genes clustered into few co-expressed groups, i.a. GR-dependent (Fkbp5, Tsc22d3, Zbtb16, Plin4) and activity-dependent (Fos, Fosl2) both upregulated in single and chronic exposure to morphine. Interestingly, 3-weeks abstinent mice didn’t exhibit any significant difference in transcription, but single dose of morphine (relapse) trigger sensitization of expression of some interesting genes (camk1g, Fosl2, Arc). CONCLUSIONS: Our results reveal that morphine induces drug‑specific transcriptional signatures in the Hip. Stress systems in Hip may modify the reward circuit through GR-dependent molecular pathways and this mechanism may be a fundamental for addiction therapy research. FINANCIAL SUPPORT: Polish National Science Centre Grant number 2013/08/A/NZ3/00848.