Background: Chloroquine is widely used in medicine. The main indication for its usage is treatment of malaria. Reports
about psychiatric side effects of chloroquine are rare. However, the list of recorded chloroquine induced neuropsychiatric
disorders shows wide range of symptoms. Aim of the work: In this study, the effect of oral chloroquine on the hippocampus of rats was assessed. Material and methods: Twenty seven male adult albino rats were randomly divided into four groups. Group I (control group): nine rats were divided into I-a and I-b subgroups. Group II (chloroquine for two weeks): six rats received 4ml of distilled water solution/day containing chloroquine in a dose of 80 mg/kg bwvia oral gavage for two weeks. Group III (chloroquine for three weeks): six rats received chloroquine as in group II for three weeks. Group IV (chloroquine for four weeks): six rats received chloroquine as in group II for four weeks. After sacrifice, the hippocampi were retrieved, fixed, and processed for paraffin sections. H&E and Bielschowsky silver stains were applied and immunehistochemical staining for GFAP was performed to examine the distribution of astrocytes. Results: Examination of different regions of the hippocampal formation revealed dark, shrunken cells, with pyknotic nuclei and pericellular spaces in all treated groups. Neurofibrillary tangles were also seen in some stained sections. Moreover, an increase in the density of astrocytes was also observed. Morphometrically, there was a decrease in the thickness of both pyramidal and granular layers of cornu ammonis and dentate gyrus respectively in all treated groups as compared with control group. All these changes appeared in group II, and were clearer in both groups III and IV. Conclusion: It was concluded that oral administration of chloroquine caused duration dependent neuronal damage in the hippocampus of rats giving a possible explanation for chloroquine induced neuropsychiatric adverse effects.