Citalopram-induced generalized lipidosis in rats

This study was focussed on the question of whether or not the potential antidepressant citalopram, which is an amphiphilic cationic compound, can induce generalized lipidosis in animals. In a short term experiment, female rats were treated with a single oral dose (100 mg/kg) and the lymph node was examined by electron microscopy; a significant number of lymphocytes showed lamellated inclusions indicating lipidosis. In a subchronic experiment (7 weeks) female rats received 140 mg/kg per day, and several organs were examined. Marked lipidosis-like alterations were found in lymph node, adrenal cortex and medulla, kidney, lung and in a sympathetic ganglion. Mild lysosomal alterations were found in hepatocytes and retinal pigment epithelium. Lipidosis was very weak, or absent, in retinal ganglion cells, trigeminal ganglion cells and in hypothalamic neurosecretory perikarya. In addition, citalopram produced myopathic alterations in soleus muscle resembling those previously induced with other cationic amphiphilic drugs. Myopathy persisted during a drug-free recovery period of 4 weeks, whereas generalized lipidosis was reversible within 2-4 weeks. The present results support a previously proposed concept concerning the structure-response relationships underlying drug-induced lipidosis.